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A Phase 1/2 Study to Evaluate MEDI4736

Sponsor
MedImmune LLC (Industry)
Overall Status
Completed
CT.gov ID
NCT01693562
Collaborator
(none)
1,022
Enrollment
79
Locations
23
Arms
89.8
Actual Duration (Months)
12.9
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a multicenter, open-label, first-time-in-human study with a standard 3+3 dose-escalation phase in participants with advanced solid tumors followed by an expansion phase in participants with advanced solid tumors. An exploration cohort has been added to determine the safety using every 4 weeks (Q4W) dosing.

Condition or Disease Intervention/Treatment Phase
Phase 1/Phase 2

Detailed Description

A dose-escalation and dose-expansion study of MEDI4736 (a monoclonal antibody that targets programmed cell death ligand-1 (PD-L1)) will evaluate the safety, tolerability, pharmacokinetics (PK), immunogenicity (IM), and antitumor activity of MEDI4736 in adult participants with solid tumors. A dose exploration cohort will look at the safety profile of Q4W dosing of MEDI4736.

Study Design

Study Type:
Interventional
Actual Enrollment :
1022 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 1/2 Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of MEDI4736 in Subjects With Advanced Solid Tumors
Actual Study Start Date :
Sep 5, 2012
Actual Primary Completion Date :
Feb 28, 2020
Actual Study Completion Date :
Feb 28, 2020

Arms and Interventions

Arm Intervention/Treatment
Experimental: Escalation Cohort (MEDI4736 0.1 mg/kg Q2W)

Participants will receive intravenous (IV) infusion of MEDI4736 (durvalumab) 0.1 mg/kg every 2 weeks (Q2W) in the dose-escalation phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first.

Drug: MEDI4736
Participants will receive IV infusion of MEDI4736 for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first.
Other Names:
  • Durvalumab

    		•
    Experimental: Escalation Cohort (MEDI4736 0.3 mg/kg Q2W)

    Participants will receive IV infusion of MEDI4736 0.3 mg/kg Q2W in the dose-escalation phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first.

    Drug: MEDI4736
    Participants will receive IV infusion of MEDI4736 for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first.
    Other Names:
  • Durvalumab

    		•
    Experimental: Escalation Cohort (MEDI4736 1 mg/kg Q2W)

    Participants will receive IV infusion of MEDI4736 1 mg/kg Q2W in the dose-escalation phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first.

    Drug: MEDI4736
    Participants will receive IV infusion of MEDI4736 for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first.
    Other Names:
  • Durvalumab

    		•
    Experimental: Escalation Cohort (MEDI4736 3 mg/kg Q2W)

    Participants will receive IV infusion of MEDI4736 3 mg/kg Q2W in the dose-escalation phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first.

    Drug: MEDI4736
    Participants will receive IV infusion of MEDI4736 for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first.
    Other Names:
  • Durvalumab

    		•
    Experimental: Escalation Cohort (MEDI4736 10 mg/kg Q2W)

    Participants will receive IV infusion of MEDI4736 10 mg/kg Q2W in the dose-escalation phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first.

    Drug: MEDI4736
    Participants will receive IV infusion of MEDI4736 for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first.
    Other Names:
  • Durvalumab

    		•
    Experimental: Escalation Cohort (MEDI4736 15 mg/kg Q3W)

    Participants will receive IV infusion of MEDI4736 15 mg/kg every 3 weeks (Q3W) in the dose-escalation phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first.

    Drug: MEDI4736
    Participants will receive IV infusion of MEDI4736 for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first.
    Other Names:
  • Durvalumab

    		•
    Experimental: Exploration Durvalumab 20 mg/kg (Q4W)

    Participants will receive IV infusion of MEDI4736 20 mg/kg every 4 weeks (Q4W) in the dose-exploration phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first.

    Drug: MEDI4736
    Participants will receive IV infusion of MEDI4736 for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first.
    Other Names:
  • Durvalumab

    		•
    Experimental: Expansion SCCHN Cohort (MEDI4736 10 mg/kg Q2W)

    Participants with squamous cell carcinoma of the head and neck (SCCHN) will receive IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first.

    Drug: MEDI4736
    Participants will receive IV infusion of MEDI4736 for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first.
    Other Names:
  • Durvalumab

    		•
    Experimental: Expansion Non-SCCHN Cohort HPV positive (MEDI4736 10 mg/kg Q2W)

    Participants with non-SCCHN human papilloma virus positive (Non-SCCHN HPV+) will receive IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first.

    Drug: MEDI4736
    Participants will receive IV infusion of MEDI4736 for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first.
    Other Names:
  • Durvalumab

    		•
    Experimental: Expansion NSCLC Cohort (MEDI4736 10 mg/kg Q2W)

    Participants with non-small-cell lung cancer (NSCLC) will receive IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first.

    Drug: MEDI4736
    Participants will receive IV infusion of MEDI4736 for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first.
    Other Names:
  • Durvalumab

    		•
    Experimental: Expansion HCC Total Cohort (MEDI4736 10 mg/kg Q2W)

    Participants with hepatocellular carcinoma (HCC Total) will receive IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first.

    Drug: MEDI4736
    Participants will receive IV infusion of MEDI4736 for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first.
    Other Names:
  • Durvalumab

    		•
    Experimental: Expansion ACM Cohort (MEDI4736 10 mg/kg Q2W)

    Participants with advance cutaneous melanoma (ACM) will receive IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first.

    Drug: MEDI4736
    Participants will receive IV infusion of MEDI4736 for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first.
    Other Names:
  • Durvalumab

    		•
    Experimental: Expansion UM Cohort (MEDI4736 10 mg/kg Q2W)

    Participants with uveal melanoma (UM) will receive IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first.

    Drug: MEDI4736
    Participants will receive IV infusion of MEDI4736 for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first.
    Other Names:
  • Durvalumab

    		•
    Experimental: Expansion GEC Cohort (MEDI4736 10 mg/kg Q2W)

    Participants with gastroesophageal cancer (GEC) will receive IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first.

    Drug: MEDI4736
    Participants will receive IV infusion of MEDI4736 for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first.
    Other Names:
  • Durvalumab

    		•
    Experimental: Expansion TNBC Cohort (MEDI4736 10 mg/kg Q2W)

    Participants with triple-negative breast cancer (TNBC) will receive IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first.

    Drug: MEDI4736
    Participants will receive IV infusion of MEDI4736 for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first.
    Other Names:
  • Durvalumab

    		•
    Experimental: Expansion PAC Cohort (MEDI4736 10 mg/kg Q2W)

    Participants with pancreatic adenocarcinoma (PAC) will receive IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first.

    Drug: MEDI4736
    Participants will receive IV infusion of MEDI4736 for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first.
    Other Names:
  • Durvalumab

    		•
    Experimental: Expansion UC Cohort (MEDI4736 10 mg/kg Q2W)

    Participants with urothelial carcinoma (UC) will receive IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first.

    Drug: MEDI4736
    Participants will receive IV infusion of MEDI4736 for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first.
    Other Names:
  • Durvalumab

    		•
    Experimental: Expansion GBM Cohort (MEDI4736 10 mg/kg Q2W)

    Participants with glioblastoma multiforme (GBM) will receive IV infusion of MEDI4736 10 mg/kg Q2W in the dose- expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first.

    Drug: MEDI4736
    Participants will receive IV infusion of MEDI4736 for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first.
    Other Names:
  • Durvalumab

    		•
    Experimental: Expansion OC Cohort (MEDI4736 10 mg/kg Q2W)

    Participants with ovarian cancer (OC) will receive IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first.

    Drug: MEDI4736
    Participants will receive IV infusion of MEDI4736 for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first.
    Other Names:
  • Durvalumab

    		•
    Experimental: Expansion STS Cohort (MEDI4736 10 mg/kg Q2W)

    Participants with soft- tissue sarcoma (STS) will receive IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first.

    Drug: MEDI4736
    Participants will receive IV infusion of MEDI4736 for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first.
    Other Names:
  • Durvalumab

    		•
    Experimental: Expansion SCLC Cohort (MEDI4736 10 mg/kg Q2W)

    Participants with small-cell lung cancer (SCLC) will receive IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first.

    Drug: MEDI4736
    Participants will receive IV infusion of MEDI4736 for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first.
    Other Names:
  • Durvalumab

    		•
    Experimental: Expansion MSI-high Cancer Cohort (MEDI4736 10 mg/kg Q2W)

    Participants with microsatellite instability (MSI)-high cancer will receive IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first.

    Drug: MEDI4736
    Participants will receive IV infusion of MEDI4736 for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first.
    Other Names:
  • Durvalumab

    		•
    Experimental: Expansion NPC Cohort (MEDI4736 10 mg/kg Q2W)

    Participants with nasopharyngeal carcinoma (NPC) will receive IV infusion of MEDI4736 10 mg/kg Q2W in the dose- expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first.

    Drug: MEDI4736
    Participants will receive IV infusion of MEDI4736 for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first.
    Other Names:
  • Durvalumab

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Number of Participants With Dose-limiting Toxicities in the Dose-escalation Phase [For MEDI4736 0.1 to MEDI4736 10 mg/kg arms: from Day 1 to Day 28 of first dose; for MEDI4736 15 mg/kg arm: from Day 1 to Day 42 of first dose]

      A DLT was defined as any Grade 3 or higher treatment-related toxicity that occurred during the DLT-evaluation period including any >= Grade 3 colitis or >= Grade 3 immune-related adverse event (irAE; AEs of immune nature in the absence of a clear alternative etiology) including rash, pruritus, or diarrhea that did not downgrade to =< Grade 2 within 3 days after onset of the event despite maximal supportive care including systemic corticosteroids. The DLT-evaluation period for 0.1 to 10 mg/kg arms was from Day 1 to Day 28 of first dose and for 15 mg/kg arm was from Day 1 to Day 42 of first dose.

    2. Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) in the Dose-escalation, Dose-exploration, and Dose-expansion Phase [From Day 1 through 90 days after the last dose of study drug (approximately 5.25 years)]

      An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. The TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug.

    3. Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in the Dose-escalation, Dose-exploration, and Dose-expansion Phase [From Day 1 through 90 days after the last dose of study drug (approximately 5.25 years)]

      Number of participants with abnormal clinical laboratory parameters reported as TEAEs are reported. Abnormal clinical laboratory parameters defined as any abnormal finding during analysis of coagulation, urine, hematology, and serum chemistry.

    4. Number of Participants With Abnormal Vital Signs Reported as TEAEs in the Dose-escalation, Dose-exploration, and Dose-expansion Phase [From Day 1 through 90 days after the last dose of study drug (approximately 5.25 years)]

      Number of participants with abnormal vital signs reported as TEAEs are reported. Abnormal vital signs are defined as any abnormal finding in the vital sign parameters (body weight, body temperature, blood pressure, pulse rate, and respiratory rate).

    5. Number of Participants With Change From Baseline in QT/QTc Interval in Local Electrocardiogram in the Dose-escalation, Dose-exploration, and Dose-expansion Phase [From Baseline (Day 1) through 90 days after the last dose of study drug (approximately 5.25 years)]

      Number of participants with change from baseline in notable QT/QTc interval in local electrocardiogram (ECG) are reported. The data for >0 participants with notable QT/QTc interval in local ECG from baseline are reported.

    6. Objective Response Rate (ORR) Assessed by Blinded Independent Central Review (BICR) in Participants With Non-squamous NSCLC Who Had Received 2 or More Prior Lines of Therapy in the Dose-expansion Phase [From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)]

      The ORR assessed by BICR in participants with non-squamous NSCLC who had received 2 or more prior lines of therapy is reported. The ORR is defined as best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR) based on Response Evaluation Criteria in Solid Tumours Version 1.1 (RECIST v1.1). The CR is defined as disappearance of all target and non-target lesions and no new lesions. A confirmed CR is defined as two CRs that were separated by at least 28 days with no evidence of progression in-between. The PR is defined as >= 30% decrease in the sum of diameters of target lesions (compared to baseline) and no new nontarget lesion. A confirmed PR is defined as two PRs or an un-confirmed PR and an un-confirmed CR that were separated by at least 4 weeks with no evidence of progression in-between.

    7. ORR Assessed by BICR in Participants With Squamous NSCLC Who Had Received 1 and 2 or More Prior Lines of Therapy in the Dose-expansion Phase [From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)]

      The ORR assessed by BICR in participants with squamous NSCLC who had received 1 and 2 or more prior lines of therapy is reported. The ORR is defined as BOR of confirmed CR or confirmed PR based on RECIST v1.1. The CR is defined as disappearance of all target and non-target lesions and no new lesions. A confirmed CR is defined as two CRs that were separated by at least 28 days with no evidence of progression in-between. The PR is defined as >= 30% decrease in the sum of diameters of target lesions (compared to baseline) and no new nontarget lesion. A confirmed PR is defined as two PRs or an un-confirmed PR and an un-confirmed CR that were separated by at least 4 weeks with no evidence of progression in-between.

    8. ORR Assessed by BICR in Participants With UC Post-platinum (Programmed Cell Death Ligand [PD-L1] Status High) Who Had Received at Least 1 Line of Prior Therapy (2L+) in the Dose-expansion Phase [From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)]

      The ORR assessed by BICR in participants with UC post-platinum PD-L1 status high 2L+ is reported. The ORR is defined as BOR of confirmed CR or confirmed PR based on RECIST v1.1. The CR is defined as disappearance of all target and non-target lesions and no new lesions. A confirmed CR is defined as two CRs that were separated by at least 28 days with no evidence of progression in-between. The PR is defined as >= 30% decrease in the sum of diameters of target lesions (compared to baseline) and no new nontarget lesion. A confirmed PR is defined as two PRs or an un-confirmed PR and an un-confirmed CR that were separated by at least 4 weeks with no evidence of progression in-between.

    Secondary Outcome Measures

    1. Area Under the Serum Concentration-time Curve up to the Last Measurable Concentration (AUClast) of MEDI4736 After the First Dose in the Dose-escalation and Dose-exploration Phase [After the first dose between Day 0 and Day 15 (Day 1 [pre and post dose] and predose of Dose 2 for all cohorts; Days 3, 5, 10 for Cohorts 0.1mg/kg to 10 mg/kg; Days 3, 5, 10, 15 for Cohort 15 mg/kg; Day 15 for Cohort 20 mg/kg)]

      Area under the concentration-time curve from time zero to the last measurable concentration (AUClast) of MEDI4736 is reported.

    2. Maximum Serum Concentration (Cmax) of MEDI4736 After the First Dose in the Dose-escalation and Dose-exploration Phase [After the first dose between Day 0 and Day 15 (Day 1 [pre and post dose] and predose of Dose 2 for all cohorts; Days 3, 5, 10 for Cohorts 0.1mg/kg to 10 mg/kg; Days 3, 5, 10, 15 for Cohort 15 mg/kg; Day 15 for Cohort 20 mg/kg)]

      The Cmax of MEDI4736 is reported.

    3. Number of Participants With Positive Anti-drug Antibodies (ADA) to MEDI4736 in the Dose-escalation, Dose-exploration Phase, and Dose-expansion Phase. [Escalation: Day1 of Dose(D)1 & D3, even numbered doses after D4; Exploration: Day1 of D1 & D2, even numbered doses after D2; Expansion: Day1 of D1, every 12 weeks since D3; all phases: till EOT, 30 days and 3 and 6 months post last dose (~5.25 years)]

      Number of participants with positive ADA titer to MEDI4736 are reported. Treatment-boosted ADA is defined as baseline positive ADA titer that was boosted to a 4-fold or higher level following drug administration; persistent positive is defined as positive at >= 2 post-baseline assessments (with >= 16 weeks between first and last positive) or positive at last post-baseline assessment; and transient positive is defined as having at least one post-baseline ADA-positive assessment and not fulfilling the condition of persistent positive.

    4. Number of Participants With Best Overall Response (BOR) Assessed by BICR in NSCLC and SCCHN Cohort in the Dose-expansion Phase [From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)]

      The BOR assessed by BICR based on RECIST v1.1 in NSCLC and SCCHN cohorts is reported. The BOR includes CR, PR, stable disease (SD), progressive disease (PD), and non-evaluable (NE). The CR is defined as disappearance of all target and non-target lesions and no new lesions. The PR is defined as >= 30% decrease in the sum of diameters of target lesions (compared to baseline) and no new nontarget lesion. The PD is defined at least 20% increase in the sum of diameters of target lesions (compared to baseline) and/or new lesion. The SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression. The NE is defined as either when no or only a subset of lesion measurements are made at an assessment.

    5. Number of Participants With BOR Assessed by Investigator in the Dose-escalation, Dose-exploration, and Dose-expansion Phase [From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)]

      The BOR assessed by investigator based on RECIST v1.1 is reported. The BOR includes CR, PR, SD, PD, and NE. The CR is defined as disappearance of all target and non-target lesions and no new lesions. The PR is defined as >= 30% decrease in the sum of diameters of target lesions (compared to baseline) and no new nontarget lesion. The PD is defined at least 20% increase in the sum of diameters of target lesions (compared to baseline) and/or new lesion. The SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression. The NE is defined as either when no or only a subset of lesion measurements are made at an assessment.

    6. Duration of Response (DoR) Assessed by BICR in NSCLC and SCCHN Cohort in the Dose-expansion Phase [From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)]

      The DoR assessed by BICR in NSCLC and SCCHN cohorts is reported. The DoR is defined as the duration from the first documentation of objective response (OR) (confirmed CR or confirmed PR) to the first documented disease progression based on RECIST v1.1 or death due to any cause, whichever occurred first. A confirmed CR is defined as two CRs (disappearance of all target and non-target lesions and no new lesions) that were separated by at least 28 days with no evidence of progression in-between. A confirmed PR is defined as two PRs (>= 30% decrease in the sum of diameters of target lesions compared to baseline and no new non-target lesion) or an un-confirmed PR and an un-confirmed CR that were separated by at least 4 weeks with no evidence of progression in-between. The DoR was estimated using Kaplan-Meier method.

    7. DoR Assessed by Investigator in the Dose-expansion Phase [From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)]

      The DoR in participants assessed by the investigator is reported. The DoR is defined as the duration from the first documentation of OR (confirmed CR or confirmed PR) to the first documented disease progression based on RECIST v1.1 or death due to any cause, whichever occurred first. A confirmed CR is defined as two CRs (disappearance of all target and non-target lesions and no new lesions) that were separated by at least 28 days with no evidence of progression in-between. A confirmed PR is defined as two PRs (>= 30% decrease in the sum of diameters of target lesions compared to baseline and no new non-target lesion) or an un-confirmed PR and an un-confirmed CR that were separated by at least 4 weeks with no evidence of progression in-between. The DoR was estimated using Kaplan-Meier method.

    8. Disease Control Rate (DCR) Assessed by BICR in NSCLC and SCCHN Cohort in the Dose-expansion Phase [From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)]

      Percentage of participants with disease control assessed by BICR in NSCLC and SCCHN cohorts is reported. Disease control is defined as a BOR of confirmed CR, confirmed PR, or SD based on RECIST v1.1. A confirmed CR is defined as two CRs (disappearance of all target and non-target lesions and no new lesions) that were separated by at least 28 days with no evidence of progression in-between. A confirmed PR is defined as two PRs (>= 30% decrease in the sum of diameters of target lesions compared to baseline and no new non-target lesion) or an un-confirmed PR and an unconfirmed CR that were separated by at least 28 days with no evidence of progression in-between. The SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression.

    9. DCR Assessed by Investigator in the Dose-expansion Phase [From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)]

      Percentage of participants with disease control assessed by the investigator is reported. Disease control is defined as a BOR of confirmed CR, confirmed PR, or SD based on RECIST v1.1. A confirmed CR is defined as two CRs (disappearance of all target and non-target lesions and no new lesions) that were separated by at least 28 days with no evidence of progression in-between. A confirmed PR is defined as two PRs (>= 30% decrease in the sum of diameters of target lesions compared to baseline and no new non-target lesion) or an un-confirmed PR and an unconfirmed CR that were separated by at least 28 days with no evidence of progression in-between. The SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression.

    10. Progression-free Survival (PFS) Assessed by BICR in NSCLC Cohort in the Dose-expansion Phase [From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)]

      The PFS assessed by BICR in NSCLC cohort is reported. The PFS is defined as the time from the start of study treatment until the first documentation of disease progression based on RECIST v1.1 or death due to any cause, whichever occurred first. The PD is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study; the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. The PFS was estimated using Kaplan-Meier method.

    11. PFS Assessed by BICR in SCCHN Cohort in the Dose-expansion Phase [From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)]

      The PFS assessed by BICR in SCCHN cohort is reported. The PFS is defined as the time from the start of study treatment until the first documentation of disease progression based on RECIST v1.1 or death due to any cause, whichever occurred first. The PD is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study; the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. The PFS was estimated using Kaplan-Meier method.

    12. PFS Assessed by Investigator in the Dose-expansion Phase [From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)]

      The PFS assessed by the investigator is reported. The PFS is defined as the time from the start of study treatment until the first documentation of disease progression based on RECIST v1.1 or death due to any cause, whichever occurred first. The PD is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study; the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. The PFS was estimated using Kaplan-Meier method.

    13. OS in the Dose-Expansion Phase [From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)]

      OS is defined as the time from the start of study treatment until death due to any cause. The OS was estimated using Kaplan-Meier method.

    14. ORR Assessed by BICR in UC Cohort (PD-L1 Low/Negative, Total, and PD-L1 High) in the Dose-expansion Phase [From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)]

      The ORR assessed by BICR in UC cohort is reported. The ORR is defined as confirmed CR or confirmed PR based on RECIST v1.1. The CR is defined as disappearance of all target and non-target lesions and no new lesions. A confirmed CR is defined as two CRs that were separated by at least 28 days with no evidence of progression in-between. The PR is defined as >= 30% decrease in the sum of diameters of target lesions (compared to baseline) and no new nontarget lesion. A confirmed PR is defined as two PRs or an un-confirmed PR and an un-confirmed CR that were separated by at least 4 weeks with no evidence of progression in-between.

    15. ORR Assessed by Investigator in UC Cohort (PD-L1 Low/Negative, Total, and PD-L1 High) in the Dose-expansion Phase [From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)]

      The ORR assessed by the investigator in UC cohort is reported. The ORR is defined as confirmed CR or confirmed PR based on RECIST v1.1. The CR is defined as disappearance of all target and non-target lesions and no new lesions. A confirmed CR is defined as two CRs that were separated by at least 28 days with no evidence of progression in-between. The PR is defined as >= 30% decrease in the sum of diameters of target lesions (compared to baseline) and no new nontarget lesion. A confirmed PR is defined as two PRs or an un-confirmed PR and an un-confirmed CR that were separated by at least 4 weeks with no evidence of progression in-between.

    16. DoR Assessed by BICR in UC Cohort (PD-L1 Low/Negative, Total, and PD-L1 High) in the Dose-expansion Phase [From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)]

      The DoR assessed by BICR in UC cohort is reported. The DoR is defined as the duration from the first documentation of OR (confirmed CR or confirmed PR) to the first documented disease progression based on RECIST v1.1 or death due to any cause, whichever occurred first. A confirmed CR is defined as two CRs (disappearance of all target and non-target lesions and no new lesions) that were separated by at least 28 days with no evidence of progression in-between. A confirmed PR is defined as two PRs (>= 30% decrease in the sum of diameters of target lesions compared to baseline and no new non-target lesion) or an un-confirmed PR and an un-confirmed CR that were separated by at least 4 weeks with no evidence of progression in-between. The DoR was estimated using Kaplan-Meier method.

    17. DoR Assessed by Investigator in UC Cohort (PD-L1 Low/Negative, Total, and PD-L1 High) in the Dose-expansion Phase [From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)]

      The DoR assessed by investigator in UC cohort is reported. The DoR is defined as the duration from the first documentation of OR (confirmed CR or confirmed PR) to the first documented disease progression based on RECIST v1.1 or death due to any cause, whichever occurred first. A confirmed CR is defined as two CRs (disappearance of all target and non-target lesions and no new lesions) that were separated by at least 28 days with no evidence of progression in-between. A confirmed PR is defined as two PRs (>= 30% decrease in the sum of diameters of target lesions compared to baseline and no new non-target lesion) or an un-confirmed PR and an un-confirmed CR that were separated by at least 4 weeks with no evidence of progression in-between. The DoR was estimated using Kaplan-Meier method.

    18. DCR Assessed by BICR in UC Cohort (PD-L1 Low/Negative, Total, and PD-L1 High) in the Dose-expansion Phase [From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)]

      Percentage of participants with disease control assessed by BICR in UC cohort is reported. The DCR is defined as a BOR of confirmed CR, confirmed PR, or SD based on RECIST v1.1. A confirmed CR is defined as two CRs (disappearance of all target and non-target lesions and no new lesions) that were separated by at least 28 days with no evidence of progression in-between. A confirmed PR is defined as two PRs (>= 30% decrease in the sum of diameters of target lesions compared to baseline and no new non-target lesion) or an un-confirmed PR and an unconfirmed CR that were separated by at least 28 days with no evidence of progression in-between. The SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression.

    19. DCR Assessed by Investigator in UC Cohort (PD-L1 Low/Negative, Total, and PD-L1 High) in the Dose-expansion Phase [From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)]

      Percentage of participants with disease control assessed by investigator in UC cohort is reported. Disease control is defined as a best overall response of confirmed CR, confirmed PR, or SD based on RECIST v1.1. A confirmed CR is defined as two CRs (disappearance of all target and non-target lesions and no new lesions) that were separated by at least 28 days with no evidence of progression in-between. A confirmed PR is defined as two PRs (>= 30% decrease in the sum of diameters of target lesions compared to baseline and no new non-target lesion) or an un-confirmed PR and an unconfirmed CR that were separated by at least 28 days with no evidence of progression in-between. The SD is defined as neither sufficient shrinkage to qualify for PR not sufficient increase to qualify for disease progression.

    20. PFS Assessed by BICR in UC Cohort (PD-L1 Low/Negative, Total, and PD-L1 High) in the Dose-expansion Phase [From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)]

      The PFS assessed by BICR in UC cohort is reported. The PFS is defined as the time from the start of study treatment until the first documentation of disease progression based on RECIST v1.1 or death due to any cause, whichever occurred first. The PD is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study; the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. The PFS was estimated using Kaplan-Meier method.

    21. PFS Assessed by Investigator in UC Cohort (PD-L1 Low/Negative, Total, and PD-L1 High) in the Dose-expansion Phase [From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)]

      The PFS assessed by the investigator in UC cohort is reported. The PFS is defined as the time from the start of study treatment until the first documentation of disease progression based on RECIST v1.1 or death due to any cause, whichever occurred first. The PD is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study; the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. The PFS was estimated using Kaplan-Meier method.

    22. OS in UC Cohort (PD-L1 Low/Negative, Total, and PD-L1 High) in the Dose-expansion Phase [From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)]

      The OS in UC cohort is reported. The OS is defined as the time from the start of study treatment until death due to any cause. The OS was estimated using Kaplan-Meier method.

    23. Adjusted Comparison of PFS by PD-L1 Status in UC Cohort in the Dose-expansion Phase [From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)]

      The PFS by PD-L1 status in UC cohort is reported. The PFS estimates are adjusted for baseline eastern cooperative oncology (ECOG), smoking status, race, gender, age, previous lines of therapy, and liver metastasis. 95% CIs based on log (-log(survival)). The PFS is defined as the time from the start of study treatment until the first documentation of disease progression based on RECIST v1.1 or death due to any cause, whichever occurred first. The PD is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study; the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. The PFS was estimated using Kaplan-Meier method.

    24. Adjusted Comparison of OS by PD-L1 Status in UC Cohort in the Dose-expansion Phase [From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)]

      The OS by PD-L1 status in UC cohort is reported. The OS estimates are adjusted for baseline ECOG, smoking status, race, gender, age, previous lines of therapy, and liver metastasis. 95% CIs based on log (-log(survival)). The OS is defined as the time from the start of study treatment until death due to any cause. The OS was estimated using Kaplan-Meier method.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 99 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Age 18 or older.

    • In the dose-escalation phase: histologically- or cytologically- confirmed advanced solid tumor that is refractory to standard therapy and for which no standard therapy exists.

    • In the dose-expansion phase: histologically- or cytologically- confirmed advanced solid tumor where if an approved first-line therapy is available, participants must have failed, be intolerant to, be ineligible for, or have refused

    • Eastern Cooperative Oncology Group (ECOG) status of 0 or 1.

    • Adequate organ and marrow function.

    • Participants must have at least 1 measurable lesion.

    • Available archived tumor tissue sample.

    • Willingness to provide consent for biopsy sample (dose-expansion only)

    Exclusion Criteria:

    • Any prior Grade ≥ 3 immune-mediated adverse event (imAE) while receiving immunotherapy

    • Prior exposure to any anti-PD-1 or anti-PD-L1 antibody

    • Any concurrent chemotherapy, immunotherapy, biologic or hormonal therapy for cancer treatment.

    • Prior treatment with immunotherapy agents including, but not limited to, tumor necrosis factor receptor superfamily agonists or checkpoint inhibitors or natural killer (NK) cell inhibitors.

    • Active or prior documented autoimmune disease within the past 2 years

    • History of primary immunodeficiency

    • History of organ transplant that requires use of immunosuppressives

    • Symptomatic or untreated central nervous system (CNS) metastases requiring concurrent treatment

    • Other invasive malignancy within 2 years

    • Women who are pregnant or lactating

    • Uncontrolled intercurrent illness

    • Known history of tuberculosis

    • Known to be human immunodeficiency virus (HIV) positive

    • Known to be Hepatitis B or C positive (except HCC participants)

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Research Site Scottsdale Arizona United States 85258
    2 Research Site Burbank California United States 91505
    3 Research Site Gilroy California United States 95020
    4 Research Site Los Angeles California United States 90025
    5 Research Site Los Angeles California United States 90095
    6 Research Site Orange California United States 92868
    7 Research Site Palo Alto California United States 94304-5826
    8 Research Site San Francisco California United States 94115
    9 Research Site Whittier California United States 90603
    10 Research Site New Haven Connecticut United States 06520
    11 Research Site Washington District of Columbia United States 20007
    12 Research Site Jacksonville Florida United States 32224
    13 Research Site Miami Beach Florida United States 33140
    14 Research Site Tampa Florida United States 33612
    15 Research Site Athens Georgia United States 30607
    16 Research Site Augusta Georgia United States 30912
    17 Research Site Chicago Illinois United States 60637
    18 Research Site Baltimore Maryland United States 21201
    19 Research Site Baltimore Maryland United States 21231
    20 Research Site Boston Massachusetts United States 02215
    21 Research Site Ann Arbor Michigan United States 48109
    22 Research Site Detroit Michigan United States 48201
    23 Research Site Minneapolis Minnesota United States 55407
    24 Research Site Saint Louis Park Minnesota United States 55416
    25 Research Site Billings Montana United States 59101
    26 Research Site Las Vegas Nevada United States 89169
    27 Research Site Hackensack New Jersey United States 07601
    28 Research Site Paterson New Jersey United States 07503
    29 Research Site Bronx New York United States 10461
    30 Research Site New York New York United States 10065
    31 Research Site Chapel Hill North Carolina United States 27599
    32 Research Site Huntersville North Carolina United States 28078
    33 Research Site Cleveland Ohio United States 44106
    34 Research Site Columbus Ohio United States 43210
    35 Research Site Portland Oregon United States 97213
    36 Research Site Philadelphia Pennsylvania United States 19107-5097
    37 Research Site Pittsburgh Pennsylvania United States 15212
    38 Research Site Greenville South Carolina United States 29605
    39 Research Site Nashville Tennessee United States 37203
    40 Research Site Dallas Texas United States 75201
    41 Research Site Houston Texas United States 77030
    42 Research Site Houston Texas United States 77090
    43 Research Site San Antonio Texas United States 78229
    44 Research Site Salt Lake City Utah United States 84403
    45 Research Site Blacksburg Virginia United States 24060
    46 Research Site Fairfax Virginia United States 22031
    47 Research Site Seattle Washington United States 98104
    48 Research Site Gent Belgium 9000
    49 Research Site Leuven Belgium 3000
    50 Research Site Liege Belgium B-4000
    51 Research Site Namur Belgium 5000
    52 Research Site Ottawa Ontario Canada K1H 8L6
    53 Research Site Toronto Ontario Canada M5G 2M9
    54 Research Site Montreal Quebec Canada H2X 3E4
    55 Research Site Paris Cedex 10 France 75475
    56 Research Site Villejuif Cedex France 94800
    57 Research Site Berlin Germany 12200
    58 Research Site Gauting Germany 82131
    59 Research Site Heidelberg Germany 69120
    60 Research Site Jena Germany 07747
    61 Research Site Minden Germany 32429
    62 Research Site Lecce Italy 73100
    63 Research Site Milano Italy 20132
    64 Research Site Milan Italy 20141
    65 Research Site Napoli Italy 80131
    66 Research Site Siena Italy 53100
    67 Research Site Gwangju Korea, Republic of 61469
    68 Research Site Seo-Gu Korea, Republic of 49241
    69 Research Site Seongnam-si Korea, Republic of 13620
    70 Research Site Seoul Korea, Republic of 03080
    71 Research Site Seoul Korea, Republic of 05505
    72 Research Site Seoul Korea, Republic of 06351
    73 Research Site Tainan Taiwan 70403
    74 Research Site Taipei Taiwan 10002
    75 Research Site London United Kingdom EC1A 7BE
    76 Research Site London United Kingdom SW2 6JJ
    77 Research Site London United Kingdom W1G 6AD
    78 Research Site Oxford United Kingdom OX3 7LE
    79 Research Site Sutton United Kingdom SM2 5PT

    Sponsors and Collaborators

    • MedImmune LLC

    Investigators

    • : MedImmune, LLC, MedImmune LLC

    Study Documents (Full-Text)

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    MedImmune LLC
    ClinicalTrials.gov Identifier:
    NCT01693562
    Other Study ID Numbers:
    • CD-ON-MEDI4736-1108
    First Posted:
    Sep 26, 2012
    Last Update Posted:
    May 13, 2021
    Last Verified:
    Apr 1, 2021
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by MedImmune LLC
    Advanced solid tumors
    Additional relevant MeSH terms:
    Durvalumab

    Study Results

    Participant Flow

    Recruitment Details The study was conducted in Belgium, Canada, France, Germany, Italy, South Korea, Taiwan, United Kingdom, and the United States of America.
    Pre-assignment Detail
    Arm/Group Title Escalation Cohort (MEDI4736 0.1 mg/kg Q2W) Escalation Cohort (MEDI4736 0.3 mg/kg Q2W) Escalation Cohort (MEDI4736 1 mg/kg Q2W) Escalation Cohort (MEDI4736 3 mg/kg Q2W) Escalation Cohort (MEDI4736 10 mg/kg Q2W) Escalation Cohort (MEDI4736 15 mg/kg Q3W) Exploration Durvalumab 20 mg/kg (Q4W) Expansion SCCHN Cohort (MEDI4736 10 mg/kg Q2W) Expansion Non-SCCHN HPV Positive Cohort (MEDI4736 10 mg/kg Q2W) Expansion NSCLC Cohort (MEDI4736 10 mg/kg Q2W) Expansion HCC Total Cohort (MEDI4736 10 mg/kg Q2W) Expansion ACM Cohort (MEDI4736 10 mg/kg Q2W) Expansion UM Cohort (MEDI4736 10 mg/kg Q2W) Expansion GEC Cohort (MEDI4736 10 mg/kg Q2W) Expansion TNBC Cohort (MEDI4736 10 mg/kg Q2W) Expansion PAC Cohort (MEDI4736 10 mg/kg Q2W) Expansion UC Cohort (MEDI4736 10 mg/kg Q2W) Expansion GBM Cohort (MEDI4736 10 mg/kg Q2W) Expansion OC Cohort (MEDI4736 10 mg/kg Q2W) Expansion STS Cohort (MEDI4736 10 mg/kg Q2W) Expansion SCLC Cohort (MEDI4736 10 mg/kg Q2W) Expansion MSI-high Cancer Cohort (MEDI4736 10 mg/kg Q2W) Expansion NPC Cohort (MEDI4736 10 mg/kg Q2W)
    Arm/Group Description Participants received intravenous (IV) infusion of MEDI4736 (durvalumab) 0.1 mg/kg every 2 weeks (Q2W) in the dose-escalation phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants received IV infusion of MEDI4736 0.3 mg/kg Q2W in the dose-escalation phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants received IV infusion of MEDI4736 1 mg/kg Q2W in the dose-escalation phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants received IV infusion of MEDI4736 3 mg/kg Q2W in the dose-escalation phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-escalation phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants received IV infusion of MEDI4736 15 mg/kg every 3 weeks (Q3W) in the dose-escalation phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants received IV infusion of MEDI4736 20 mg/kg every 4 weeks (Q4W) in the dose-exploration phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with squamous cell carcinoma of the head and neck (SCCHN) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with non-SCCHN human papilloma virus positive (Non-SCCHN HPV+) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with non-small-cell lung cancer (NSCLC) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with hepatocellular carcinoma (HCC Total) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with advance cutaneous melanoma (ACM) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with uveal melanoma (UM) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with gastroesophageal cancer (GEC) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with triple-negative breast cancer (TNBC) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with pancreatic adenocarcinoma (PAC) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with urothelial carcinoma (UC) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with glioblastoma multiforme (GBM) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose- expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with ovarian cancer (OC) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with soft- tissue sarcoma (STS) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with small-cell lung cancer (SCLC) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with microsatellite instability (MSI)-high cancer received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with nasopharyngeal carcinoma (NPC) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose- expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.
    Period Title: Escalation Phase
    STARTED 4 4 3 3 6 7 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
    COMPLETED 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
    NOT COMPLETED 4 4 3 3 6 7 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
    Period Title: Escalation Phase
    STARTED 0 0 0 0 0 0 21 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
    COMPLETED 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
    NOT COMPLETED 0 0 0 0 0 0 21 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
    Period Title: Escalation Phase
    STARTED 0 0 0 0 0 0 0 62 22 304 40 21 24 51 40 31 201 20 47 20 21 62 10
    COMPLETED 0 0 0 0 0 0 0 0 0 4 0 0 1 0 0 0 4 0 0 0 0 0 0
    NOT COMPLETED 0 0 0 0 0 0 0 62 22 300 40 21 23 51 40 31 197 20 47 20 21 62 10

    Baseline Characteristics

    Arm/Group Title Escalation Cohort (MEDI4736 0.1 mg/kg Q2W) Escalation Cohort (MEDI4736 0.3 mg/kg Q2W) Escalation Cohort (MEDI4736 1 mg/kg Q2W) Escalation Cohort (MEDI4736 3 mg/kg Q2W) Escalation Cohort (MEDI4736 10 mg/kg Q2W) Escalation Cohort (MEDI4736 15 mg/kg Q3W) Exploration Durvalumab 20 mg/kg (Q4W) Expansion SCCHN Cohort (MEDI4736 10 mg/kg Q2W) Expansion Non-SCCHN HPV Positive Cohort (MEDI4736 10 mg/kg Q2W) Expansion NSCLC Cohort (MEDI4736 10 mg/kg Q2W) Expansion HCC Total Cohort (MEDI4736 10 mg/kg Q2W) Expansion ACM Cohort (MEDI4736 10 mg/kg Q2W) Expansion UM Cohort (MEDI4736 10 mg/kg Q2W) Expansion GEC Cohort (MEDI4736 10 mg/kg Q2W) Expansion TNBC Cohort (MEDI4736 10 mg/kg Q2W) Expansion PAC Cohort (MEDI4736 10 mg/kg Q2W) Expansion UC Cohort (MEDI4736 10 mg/kg Q2W) Expansion GBM Cohort (MEDI4736 10 mg/kg Q2W) Expansion OC Cohort (MEDI4736 10 mg/kg Q2W) Expansion STS Cohort (MEDI4736 10 mg/kg Q2W) Expansion SCLC Cohort (MEDI4736 10 mg/kg Q2W) Expansion MSI-high Cancer Cohort (MEDI4736 10 mg/kg Q2W) Expansion NPC Cohort (MEDI4736 10 mg/kg Q2W) Total
    Arm/Group Description Participants received intravenous (IV) infusion of MEDI4736 (durvalumab) 0.1 mg/kg every 2 weeks (Q2W) in the dose-escalation phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants received IV infusion of MEDI4736 0.3 mg/kg Q2W in the dose-escalation phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants received IV infusion of MEDI4736 1 mg/kg Q2W in the dose-escalation phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants received IV infusion of MEDI4736 3 mg/kg Q2W in the dose-escalation phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-escalation phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants received IV infusion of MEDI4736 15 mg/kg every 3 weeks (Q3W) in the dose-escalation phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants received IV infusion of MEDI4736 20 mg/kg every 4 weeks (Q4W) in the dose-exploration phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with squamous cell carcinoma of the head and neck (SCCHN) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with non-SCCHN human papilloma virus positive (Non-SCCHN HPV+) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with non-small-cell lung cancer (NSCLC) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with hepatocellular carcinoma (HCC Total) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with advance cutaneous melanoma (ACM) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with uveal melanoma (UM) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with gastroesophageal cancer (GEC) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with triple-negative breast cancer (TNBC) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with pancreatic adenocarcinoma (PAC) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with urothelial carcinoma (UC) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with glioblastoma multiforme (GBM) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose- expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with ovarian cancer (OC) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with soft- tissue sarcoma (STS) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with small-cell lung cancer (SCLC) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with microsatellite instability (MSI)-high cancer received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with nasopharyngeal carcinoma (NPC) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose- expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Total of all reporting groups
    Overall Participants 4 4 3 3 6 7 21 62 22 304 40 21 24 51 40 31 201 20 47 20 21 62 10 1024
    Age, Customized (Count of Participants)
    18-64 years
    2
    50%
    0
    0%
    1
    33.3%
    2
    66.7%
    6
    100%
    4
    57.1%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    15
    1.5%
    65-84 years
    2
    50%
    4
    100%
    2
    66.7%
    1
    33.3%
    0
    0%
    3
    42.9%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    12
    1.2%
    85 years and above
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    18-64 years
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    12
    57.1%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    12
    1.2%
    65-84 years
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    9
    42.9%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    9
    0.9%
    85 years and above
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    18-64 years
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    41
    66.1%
    19
    86.4%
    146
    48%
    26
    65%
    12
    57.1%
    14
    58.3%
    33
    64.7%
    35
    87.5%
    16
    51.6%
    77
    38.3%
    16
    80%
    30
    63.8%
    15
    75%
    9
    42.9%
    47
    75.8%
    7
    70%
    543
    53%
    65-84 years
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    20
    32.3%
    3
    13.6%
    156
    51.3%
    14
    35%
    9
    42.9%
    10
    41.7%
    18
    35.3%
    5
    12.5%
    15
    48.4%
    122
    60.7%
    4
    20%
    16
    34%
    5
    25%
    12
    57.1%
    15
    24.2%
    3
    30%
    427
    41.7%
    85 years and above
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    1.6%
    0
    0%
    2
    0.7%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    2
    1%
    0
    0%
    1
    2.1%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    6
    0.6%
    Sex: Female, Male (Count of Participants)
    Female
    2
    50%
    1
    25%
    2
    66.7%
    2
    66.7%
    2
    33.3%
    2
    28.6%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    11
    1.1%
    Male
    2
    50%
    3
    75%
    1
    33.3%
    1
    33.3%
    4
    66.7%
    5
    71.4%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    16
    1.6%
    Female
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    5
    23.8%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    5
    0.5%
    Male
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    16
    76.2%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    16
    1.6%
    Female
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    9
    14.5%
    15
    68.2%
    133
    43.8%
    8
    20%
    9
    42.9%
    10
    41.7%
    13
    25.5%
    40
    100%
    9
    29%
    58
    28.9%
    7
    35%
    47
    100%
    15
    75%
    8
    38.1%
    34
    54.8%
    3
    30%
    418
    40.8%
    Male
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    53
    85.5%
    7
    31.8%
    171
    56.3%
    32
    80%
    12
    57.1%
    14
    58.3%
    38
    74.5%
    0
    0%
    22
    71%
    143
    71.1%
    13
    65%
    0
    0%
    5
    25%
    13
    61.9%
    28
    45.2%
    7
    70%
    558
    54.5%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    1
    25%
    0
    0%
    0
    0%
    0
    0%
    1
    16.7%
    1
    14.3%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    3
    0.3%
    Not Hispanic or Latino
    3
    75%
    4
    100%
    2
    66.7%
    3
    100%
    5
    83.3%
    6
    85.7%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    23
    2.2%
    Unknown or Not Reported
    0
    0%
    0
    0%
    1
    33.3%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    0.1%
    Hispanic or Latino
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    2
    9.5%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    2
    0.2%
    Not Hispanic or Latino
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    19
    90.5%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    19
    1.9%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Hispanic or Latino
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    5
    8.1%
    1
    4.5%
    12
    3.9%
    2
    5%
    2
    9.5%
    1
    4.2%
    4
    7.8%
    0
    0%
    1
    3.2%
    5
    2.5%
    2
    10%
    2
    4.3%
    5
    25%
    1
    4.8%
    4
    6.5%
    0
    0%
    47
    4.6%
    Not Hispanic or Latino
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    54
    87.1%
    21
    95.5%
    287
    94.4%
    32
    80%
    19
    90.5%
    18
    75%
    43
    84.3%
    33
    82.5%
    30
    96.8%
    177
    88.1%
    18
    90%
    39
    83%
    15
    75%
    20
    95.2%
    42
    67.7%
    10
    100%
    858
    83.8%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    3
    4.8%
    0
    0%
    5
    1.6%
    6
    15%
    0
    0%
    5
    20.8%
    4
    7.8%
    7
    17.5%
    0
    0%
    19
    9.5%
    0
    0%
    6
    12.8%
    0
    0%
    0
    0%
    16
    25.8%
    0
    0%
    71
    6.9%
    Race/Ethnicity, Customized (Count of Participants)
    American Indian or Alaskan Native
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Asian
    0
    0%
    0
    0%
    0
    0%
    1
    33.3%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    0.1%
    Black or African American
    0
    0%
    1
    25%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    0.1%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    White
    4
    100%
    3
    75%
    2
    66.7%
    2
    66.7%
    6
    100%
    7
    100%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    24
    2.3%
    Other
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Multiple
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Missing
    0
    0%
    0
    0%
    1
    33.3%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    0.1%
    American Indian or Alaskan Native
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Asian
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    4.8%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    0.1%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    White
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    19
    90.5%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    19
    1.9%
    Other
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    4.8%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    0.1%
    Multiple
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Missing
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    American Indian or Alaskan Native
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Asian
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    5
    8.1%
    1
    4.5%
    58
    19.1%
    9
    22.5%
    0
    0%
    0
    0%
    1
    2%
    2
    5%
    0
    0%
    40
    19.9%
    0
    0%
    4
    8.5%
    1
    5%
    2
    9.5%
    6
    9.7%
    5
    50%
    134
    13.1%
    Black or African American
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    1.6%
    2
    9.1%
    10
    3.3%
    3
    7.5%
    1
    4.8%
    0
    0%
    1
    2%
    6
    15%
    1
    3.2%
    8
    4%
    0
    0%
    1
    2.1%
    1
    5%
    1
    4.8%
    2
    3.2%
    0
    0%
    38
    3.7%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    1.6%
    0
    0%
    0
    0%
    2
    5%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    2
    20%
    5
    0.5%
    White
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    49
    79%
    19
    86.4%
    227
    74.7%
    19
    47.5%
    19
    90.5%
    19
    79.2%
    45
    88.2%
    25
    62.5%
    29
    93.5%
    128
    63.7%
    19
    95%
    36
    76.6%
    18
    90%
    17
    81%
    34
    54.8%
    3
    30%
    706
    68.9%
    Other
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    2
    3.2%
    0
    0%
    4
    1.3%
    1
    2.5%
    0
    0%
    0
    0%
    0
    0%
    1
    2.5%
    1
    3.2%
    5
    2.5%
    1
    5%
    0
    0%
    0
    0%
    1
    4.8%
    4
    6.5%
    0
    0%
    20
    2%
    Multiple
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    2%
    0
    0%
    0
    0%
    1
    0.5%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    2
    0.2%
    Missing
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    4
    6.5%
    0
    0%
    5
    1.6%
    6
    15%
    1
    4.8%
    5
    20.8%
    3
    5.9%
    6
    15%
    0
    0%
    19
    9.5%
    0
    0%
    6
    12.8%
    0
    0%
    0
    0%
    16
    25.8%
    0
    0%
    71
    6.9%

    Outcome Measures

    1. Primary Outcome
    Title Number of Participants With Dose-limiting Toxicities in the Dose-escalation Phase
    Description A DLT was defined as any Grade 3 or higher treatment-related toxicity that occurred during the DLT-evaluation period including any >= Grade 3 colitis or >= Grade 3 immune-related adverse event (irAE; AEs of immune nature in the absence of a clear alternative etiology) including rash, pruritus, or diarrhea that did not downgrade to =< Grade 2 within 3 days after onset of the event despite maximal supportive care including systemic corticosteroids. The DLT-evaluation period for 0.1 to 10 mg/kg arms was from Day 1 to Day 28 of first dose and for 15 mg/kg arm was from Day 1 to Day 42 of first dose.
    Time Frame For MEDI4736 0.1 to MEDI4736 10 mg/kg arms: from Day 1 to Day 28 of first dose; for MEDI4736 15 mg/kg arm: from Day 1 to Day 42 of first dose

    Outcome Measure Data

    Analysis Population Description
    DLT-evaluable population included all participants in the dose-escalation phase who received at least 2 doses of study drug and completed safety follow-up through DLT-evaluable period or experienced any DLT during the DLT-evaluation period.
    Arm/Group Title Escalation Cohort (MEDI4736 0.1 mg/kg Q2W) Escalation Cohort (MEDI4736 0.3 mg/kg Q2W) Escalation Cohort (MEDI4736 1 mg/kg Q2W) Escalation Cohort (MEDI4736 3 mg/kg Q2W) Escalation Cohort (MEDI4736 10 mg/kg Q2W) Escalation Cohort (MEDI4736 15 mg/kg Q3W)
    Arm/Group Description Participants received intravenous (IV) infusion of MEDI4736 (durvalumab) 0.1 mg/kg every 2 weeks (Q2W) in the dose-escalation phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants received IV infusion of MEDI4736 0.3 mg/kg Q2W in the dose-escalation phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation , whichever occurred first Participants received IV infusion of MEDI4736 1 mg/kg Q2W in the dose-escalation phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants received IV infusion of MEDI4736 3 mg/kg Q2W in the dose-escalation phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation , whichever occurred first. Participants received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-escalation phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation , whichever occurred first. Participants received IV infusion of MEDI4736 15 mg/kg every 3 weeks (Q3W) in the dose-escalation phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.
    Measure Participants 4 4 3 3 6 7
    Count of Participants [Participants]
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    2. Primary Outcome
    Title Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) in the Dose-escalation, Dose-exploration, and Dose-expansion Phase
    Description An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. The TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug.
    Time Frame From Day 1 through 90 days after the last dose of study drug (approximately 5.25 years)

    Outcome Measure Data

    Analysis Population Description
    As-treated population included all participants who received any dose of study drug. Participants enrolled in the 10 mg/kg Q2W Expansion and Escalation Cohort have been summarized as a total only. This is because the safety profile of durvalumab monotherapy 10 mg/kg Q2W was manageable and generally consistent with the known safety profile of the anti-programmed cell death ligand (PD-L1/PD-1) drug class.
    Arm/Group Title Escalation Cohort (MEDI4736 0.1 mg/kg Q2W) Escalation Cohort (MEDI4736 0.3 mg/kg Q2W) Escalation Cohort (MEDI4736 1 mg/kg Q2W) Escalation Cohort (MEDI4736 3 mg/kg Q2W) Escalation Cohort (MEDI4736 15 mg/kg Q3W) Exploration Cohort (MEDI4736 20 mg/kg Q4W) Escalation/Expansion Cohort (Total MEDI4736 10 mg/kg Q2W)
    Arm/Group Description Participants received intravenous (IV) infusion of MEDI4736 (durvalumab) 0.1 mg/kg every 2 weeks (Q2W) in the dose-escalation phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants received IV infusion of MEDI4736 0.3 mg/kg Q2W in the dose-escalation phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation , whichever occurred first Participants received IV infusion of MEDI4736 1 mg/kg Q2W in the dose-escalation phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants received IV infusion of MEDI4736 3 mg/kg Q2W in the dose-escalation phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation , whichever occurred first. Participants received IV infusion of MEDI4736 15 mg/kg every 3 weeks (Q3W) in the dose-escalation phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants received IV infusion of MEDI4736 20 mg/kg every 4 weeks (Q4W) in the dose-exploration phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-escalation or dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation , whichever occurred first.
    Measure Participants 4 4 3 3 7 21 980
    Any TEAEs
    3
    75%
    4
    100%
    3
    100%
    3
    100%
    7
    116.7%
    21
    300%
    963
    4585.7%
    Any TESAEs
    1
    25%
    2
    50%
    1
    33.3%
    1
    33.3%
    3
    50%
    13
    185.7%
    536
    2552.4%
    3. Primary Outcome
    Title Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in the Dose-escalation, Dose-exploration, and Dose-expansion Phase
    Description Number of participants with abnormal clinical laboratory parameters reported as TEAEs are reported. Abnormal clinical laboratory parameters defined as any abnormal finding during analysis of coagulation, urine, hematology, and serum chemistry.
    Time Frame From Day 1 through 90 days after the last dose of study drug (approximately 5.25 years)

    Outcome Measure Data

    Analysis Population Description
    As-treated population included all participants who received any dose of study drug. Participants enrolled in the 10 mg/kg Q2W Expansion and Escalation Cohort have been summarized as a total only. This is because the safety profile of durvalumab monotherapy 10 mg/kg Q2W was manageable and generally consistent with the known safety profile of the anti-PD-L1/PD-1 drug class.
    Arm/Group Title Escalation Cohort (MEDI4736 0.1 mg/kg Q2W) Escalation Cohort (MEDI4736 0.3 mg/kg Q2W) Escalation Cohort (MEDI4736 1 mg/kg Q2W) Escalation Cohort (MEDI4736 3 mg/kg Q2W) Escalation Cohort (MEDI4736 15 mg/kg Q3W) Exploration Cohort (MEDI4736 20 mg/kg Q4W) Escalation/Expansion Cohort (Total MEDI4736 10 mg/kg Q2W)
    Arm/Group Description Participants received intravenous (IV) infusion of MEDI4736 (durvalumab) 0.1 mg/kg every 2 weeks (Q2W) in the dose-escalation phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants received IV infusion of MEDI4736 0.3 mg/kg Q2W in the dose-escalation phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation , whichever occurred first Participants received IV infusion of MEDI4736 1 mg/kg Q2W in the dose-escalation phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants received IV infusion of MEDI4736 3 mg/kg Q2W in the dose-escalation phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation , whichever occurred first. Participants received IV infusion of MEDI4736 15 mg/kg every 3 weeks (Q3W) in the dose-escalation phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants received IV infusion of MEDI4736 20 mg/kg every 4 weeks (Q4W) in the dose-exploration phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-escalation or dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation , whichever occurred first.
    Measure Participants 4 4 3 3 7 21 980
    Anaemia
    1
    25%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    166
    790.5%
    Thrombocytopenia
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    14.3%
    24
    114.3%
    White blood cell count increased
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    14.3%
    3
    14.3%
    Leukocytosis
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    20
    95.2%
    Lymphocyte count decreased
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    12
    57.1%
    Neutropenia
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    8
    38.1%
    Leukopenia
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    7
    33.3%
    Thrombocytosis
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    5
    23.8%
    Iron deficiency anaemia
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    3
    14.3%
    Haemoglobin decreased
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    2
    9.5%
    Neutrophil count increased
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    2
    9.5%
    Red blood cell count decreased
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    4.8%
    Anaemia of chronic disease
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    4.8%
    Eosinophilia
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    4.8%
    Haemolysis
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    4.8%
    Leukostasis syndrome
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    4.8%
    Immune thrombocytopenic purpura
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    4.8%
    International normalised ratio increased
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    16
    76.2%
    Activated partial thromboplastin time prolonged
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    15
    71.4%
    Blood fibrinogen increased
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    8
    38.1%
    Platelet count decreased
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    5
    23.8%
    Disseminated intravascular coagulation
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    2
    9.5%
    Prothrombin time prolonged
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    2
    9.5%
    Activated partial thromboplastin time shortened
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    4.8%
    Coagulation factor increased
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    4.8%
    Coagulopathy
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    4.8%
    Alanine aminotransferase increased
    0
    0%
    0
    0%
    1
    33.3%
    0
    0%
    1
    16.7%
    2
    28.6%
    77
    366.7%
    Aspartate aminotransferase increased
    0
    0%
    0
    0%
    1
    33.3%
    0
    0%
    1
    16.7%
    2
    28.6%
    99
    471.4%
    Blood alkaline phosphatase increased
    0
    0%
    0
    0%
    1
    33.3%
    0
    0%
    0
    0%
    1
    14.3%
    70
    333.3%
    Blood bilirubin increased
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    14.3%
    42
    200%
    Gamma-glutamyltransferase increased
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    2
    28.6%
    71
    338.1%
    Hyperbilirubinaemia
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    14
    66.7%
    Transaminases increased
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    8
    38.1%
    Blood lactate dehydrogenase increased
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    7
    33.3%
    Hepatic function abnormal
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    6
    28.6%
    Alanine aminotransferase decreased
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    4.8%
    Aspartate aminotransferase decreased
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    4.8%
    Blood albumin decreased
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    4.8%
    Hepatic enzyme increased
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    4.8%
    Liver function test increased
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    4.8%
    White blood cell count decreased
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    8
    38.1%
    Neutrophil count decreased
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    5
    23.8%
    Lymphopenia
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    5
    23.8%
    Blood creatinine increased
    0
    0%
    1
    25%
    1
    33.3%
    0
    0%
    0
    0%
    0
    0%
    46
    219%
    Hyperuricaemia
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    22
    104.8%
    Blood urea increased
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    10
    47.6%
    Glomerular filtration rate decreased
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    2
    9.5%
    Hypothyroidism
    0
    0%
    1
    25%
    1
    33.3%
    0
    0%
    1
    16.7%
    3
    42.9%
    89
    423.8%
    Hyperthyroidism
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    14.3%
    30
    142.9%
    Blood thyroid stimulating hormone increased
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    16
    76.2%
    Blood thyroid stimulating hormone decreased
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    5
    23.8%
    Thyroxine decreased
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    2
    9.5%
    Thyroxine free decreased
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    2
    9.5%
    Thyroxine free increased
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    2
    9.5%
    Tri-iodothyronine free decreased
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    2
    9.5%
    Thyroxine increased
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    4.8%
    Tri-iodothyronine decreased
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    4.8%
    Tri-iodothyronine increased
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    4.8%
    Hyponatraemia
    0
    0%
    0
    0%
    1
    33.3%
    0
    0%
    1
    16.7%
    1
    14.3%
    91
    433.3%
    Hypomagnesaemia
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    14.3%
    55
    261.9%
    Hypercalcaemia
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    47
    223.8%
    Hyperglycaemia
    0
    0%
    0
    0%
    1
    33.3%
    0
    0%
    0
    0%
    0
    0%
    32
    152.4%
    Hypokalaemia
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    60
    285.7%
    Hypocalcaemia
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    17
    81%
    Hypophosphataemia
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    16
    76.2%
    Hypertriglyceridaemia
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    13
    61.9%
    Hypoglycaemia
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    10
    47.6%
    Blood cholesterol increased
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    6
    28.6%
    Blood magnesium decreased
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    5
    23.8%
    Blood triglycerides increased
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    5
    23.8%
    Blood glucose increased
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    4
    19%
    Hypercholesterolaemia
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    4
    19%
    Blood potassium increased
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    3
    14.3%
    Blood chloride increased
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    2
    9.5%
    Blood electrolytes decreased
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    2
    9.5%
    Blood potassium decreased
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    2
    9.5%
    Hyperphosphataemia
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    2
    9.5%
    Protein total decreased
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    2
    9.5%
    Protein urine present
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    2
    9.5%
    Blood bicarbonate decreased
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    4.8%
    Blood chloride decreased
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    4.8%
    Blood sodium decreased
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    4.8%
    Hypermagnesaemia
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    4.8%
    Hypernatraemia
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    4.8%
    Hypochloraemia
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    4.8%
    Hypoproteinaemia
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    4.8%
    Hyperkalaemia
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    30
    142.9%
    4. Primary Outcome
    Title Number of Participants With Abnormal Vital Signs Reported as TEAEs in the Dose-escalation, Dose-exploration, and Dose-expansion Phase
    Description Number of participants with abnormal vital signs reported as TEAEs are reported. Abnormal vital signs are defined as any abnormal finding in the vital sign parameters (body weight, body temperature, blood pressure, pulse rate, and respiratory rate).
    Time Frame From Day 1 through 90 days after the last dose of study drug (approximately 5.25 years)

    Outcome Measure Data

    Analysis Population Description
    As-treated population included all participants who received any dose of study drug. Participants enrolled in the 10 mg/kg Q2W Expansion and Escalation Cohort have been summarized as a total only. This is because the safety profile of durvalumab monotherapy 10 mg/kg Q2W was manageable and generally consistent with the known safety profile of the anti-PD-L1/PD-1 drug class.
    Arm/Group Title Escalation Cohort (MEDI4736 0.1 mg/kg Q2W) Escalation Cohort (MEDI4736 0.3 mg/kg Q2W) Escalation Cohort (MEDI4736 1 mg/kg Q2W) Escalation Cohort (MEDI4736 3 mg/kg Q2W) Escalation Cohort (MEDI4736 15 mg/kg Q3W) Exploration Cohort (MEDI4736 20 mg/kg Q4W) Escalation/Expansion Cohort (Total MEDI4736 10 mg/kg Q2W)
    Arm/Group Description Participants received intravenous (IV) infusion of MEDI4736 (durvalumab) 0.1 mg/kg every 2 weeks (Q2W) in the dose-escalation phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants received IV infusion of MEDI4736 0.3 mg/kg Q2W in the dose-escalation phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation , whichever occurred first Participants received IV infusion of MEDI4736 1 mg/kg Q2W in the dose-escalation phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants received IV infusion of MEDI4736 3 mg/kg Q2W in the dose-escalation phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation , whichever occurred first. Participants received IV infusion of MEDI4736 15 mg/kg every 3 weeks (Q3W) in the dose-escalation phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants received IV infusion of MEDI4736 20 mg/kg every 4 weeks (Q4W) in the dose-exploration phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-escalation or dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation , whichever occurred first.
    Measure Participants 4 4 3 3 7 21 980
    Pyrexia
    0
    0%
    3
    75%
    0
    0%
    1
    33.3%
    3
    50%
    2
    28.6%
    145
    690.5%
    Weight decreased
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    2
    28.6%
    79
    376.2%
    Hypertension
    0
    0%
    1
    25%
    0
    0%
    1
    33.3%
    0
    0%
    0
    0%
    31
    147.6%
    Hypotension
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    14.3%
    36
    171.4%
    Weight increased
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    22
    104.8%
    Tachycardia
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    19
    90.5%
    Sinus tachycardia
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    14
    66.7%
    Arrhythmia
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    3
    14.3%
    Sinus bradycardia
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    3
    14.3%
    Heart rate increased
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    4.8%
    Heart rate irregular
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    4.8%
    Peak expiratory flow rate decreased
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    4.8%
    5. Primary Outcome
    Title Number of Participants With Change From Baseline in QT/QTc Interval in Local Electrocardiogram in the Dose-escalation, Dose-exploration, and Dose-expansion Phase
    Description Number of participants with change from baseline in notable QT/QTc interval in local electrocardiogram (ECG) are reported. The data for >0 participants with notable QT/QTc interval in local ECG from baseline are reported.
    Time Frame From Baseline (Day 1) through 90 days after the last dose of study drug (approximately 5.25 years)

    Outcome Measure Data

    Analysis Population Description
    As-treated population included all participants who received any dose of study drug were analyzed. Participants with ECG readings available were evaluable for this analysis. Participants enrolled in the 10 mg/kg Q2W Expansion and Escalation Cohort have been summarized as a total only. This is because the safety profile of durvalumab monotherapy 10 mg/kg Q2W was manageable and generally consistent with the known safety profile of the anti-PD-L1/PD-1 drug class.
    Arm/Group Title Escalation Cohort (MEDI4736 0.1 mg/kg Q2W) Escalation Cohort (MEDI4736 0.3 mg/kg Q2W) Escalation Cohort (MEDI4736 1 mg/kg Q2W) Escalation Cohort (MEDI4736 3 mg/kg Q2W) Escalation Cohort (MEDI4736 15 mg/kg Q3W) Exploration Cohort (MEDI4736 20 mg/kg Q4W) Escalation/Expansion Cohort (Total MEDI4736 10 mg/kg Q2W)
    Arm/Group Description Participants received intravenous (IV) infusion of MEDI4736 (durvalumab) 0.1 mg/kg every 2 weeks (Q2W) in the dose-escalation phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants received IV infusion of MEDI4736 0.3 mg/kg Q2W in the dose-escalation phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation , whichever occurred first Participants received IV infusion of MEDI4736 1 mg/kg Q2W in the dose-escalation phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants received IV infusion of MEDI4736 3 mg/kg Q2W in the dose-escalation phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation , whichever occurred first. Participants received IV infusion of MEDI4736 15 mg/kg every 3 weeks (Q3W) in the dose-escalation phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants received IV infusion of MEDI4736 20 mg/kg every 4 weeks (Q4W) in the dose-exploration phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-escalation or dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation , whichever occurred first.
    Measure Participants 4 4 3 3 7 21 980
    QTcF: > 30 (msec)
    1
    25%
    0
    0%
    0
    0%
    4
    133.3%
    QTcF: > 60 (msec)
    1
    25%
    0
    0%
    0
    0%
    0
    0%
    QTcB: > 30 (msec)
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    4
    57.1%
    17
    81%
    QTcB: > 60 (msec)
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    4
    19%
    QTcB: > 90 (msec)
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    3
    14.3%
    6. Primary Outcome
    Title Objective Response Rate (ORR) Assessed by Blinded Independent Central Review (BICR) in Participants With Non-squamous NSCLC Who Had Received 2 or More Prior Lines of Therapy in the Dose-expansion Phase
    Description The ORR assessed by BICR in participants with non-squamous NSCLC who had received 2 or more prior lines of therapy is reported. The ORR is defined as best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR) based on Response Evaluation Criteria in Solid Tumours Version 1.1 (RECIST v1.1). The CR is defined as disappearance of all target and non-target lesions and no new lesions. A confirmed CR is defined as two CRs that were separated by at least 28 days with no evidence of progression in-between. The PR is defined as >= 30% decrease in the sum of diameters of target lesions (compared to baseline) and no new nontarget lesion. A confirmed PR is defined as two PRs or an un-confirmed PR and an un-confirmed CR that were separated by at least 4 weeks with no evidence of progression in-between.
    Time Frame From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)

    Outcome Measure Data

    Analysis Population Description
    Participants with non-squamous NSCLC in Full analysis set (FAS) population who had received 2 or more prior line of therapy were analyzed. FAS population included all participants who received any dose of study drug, had measurable disease at baseline (Day 1) per BICR and were followed for at least 24 weeks by 16Oct2017.
    Arm/Group Title Expansion Non-squamous NSCLC 3L+ Cohort
    Arm/Group Description Participants with non-squamous NSCLC who had received 2 or more lines of prior therapy (3L+) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.
    Measure Participants 68
    Number (95% Confidence Interval) [Percentage of participants]
    10.3
    257.5%
    7. Primary Outcome
    Title ORR Assessed by BICR in Participants With Squamous NSCLC Who Had Received 1 and 2 or More Prior Lines of Therapy in the Dose-expansion Phase
    Description The ORR assessed by BICR in participants with squamous NSCLC who had received 1 and 2 or more prior lines of therapy is reported. The ORR is defined as BOR of confirmed CR or confirmed PR based on RECIST v1.1. The CR is defined as disappearance of all target and non-target lesions and no new lesions. A confirmed CR is defined as two CRs that were separated by at least 28 days with no evidence of progression in-between. The PR is defined as >= 30% decrease in the sum of diameters of target lesions (compared to baseline) and no new nontarget lesion. A confirmed PR is defined as two PRs or an un-confirmed PR and an un-confirmed CR that were separated by at least 4 weeks with no evidence of progression in-between.
    Time Frame From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)

    Outcome Measure Data

    Analysis Population Description
    Participants with squamous NSCLC in FAS population who had received 1 and 2 or more prior lines of therapy were analyzed. FAS population included all participants who received any dose of study drug, had measurable disease at baseline (Day 1) per BICR and were followed for at least 24 weeks by 16Oct2017.
    Arm/Group Title Expansion Squamous NSCLC 2L+ Cohort Expansion Squamous NSCLC 3L+ Cohort
    Arm/Group Description Participants with squamous NSCLC who had received at least 1 line of prior therapy (2L+) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with squamous NSCLC who had received 2 or more lines of prior therapy (3L+) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.
    Measure Participants 117 62
    Number (95% Confidence Interval) [Percentage of participants]
    12.8
    320%
    12.9
    322.5%
    8. Primary Outcome
    Title ORR Assessed by BICR in Participants With UC Post-platinum (Programmed Cell Death Ligand [PD-L1] Status High) Who Had Received at Least 1 Line of Prior Therapy (2L+) in the Dose-expansion Phase
    Description The ORR assessed by BICR in participants with UC post-platinum PD-L1 status high 2L+ is reported. The ORR is defined as BOR of confirmed CR or confirmed PR based on RECIST v1.1. The CR is defined as disappearance of all target and non-target lesions and no new lesions. A confirmed CR is defined as two CRs that were separated by at least 28 days with no evidence of progression in-between. The PR is defined as >= 30% decrease in the sum of diameters of target lesions (compared to baseline) and no new nontarget lesion. A confirmed PR is defined as two PRs or an un-confirmed PR and an un-confirmed CR that were separated by at least 4 weeks with no evidence of progression in-between.
    Time Frame From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)

    Outcome Measure Data

    Analysis Population Description
    Participants with UC in FAS population with 2L+ post-platinum PD-L1 status high (>= 25% tumor cell membrane or >= 25% immune cell staining) were analyzed. FAS population included all participants who received any dose of study drug, had measurable disease at baseline (Day 1) per BICR and were followed for at least 24 weeks by 16Oct2017.
    Arm/Group Title Expansion UC PD-L1 High 2L+ Cohort
    Arm/Group Description Participants with UC (post-platinum PD-L1 status high) who had received at least 1 line of prior therapy (2L+) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.
    Measure Participants 98
    Number (95% Confidence Interval) [Percentage of participants]
    27.6
    690%
    9. Secondary Outcome
    Title Area Under the Serum Concentration-time Curve up to the Last Measurable Concentration (AUClast) of MEDI4736 After the First Dose in the Dose-escalation and Dose-exploration Phase
    Description Area under the concentration-time curve from time zero to the last measurable concentration (AUClast) of MEDI4736 is reported.
    Time Frame After the first dose between Day 0 and Day 15 (Day 1 [pre and post dose] and predose of Dose 2 for all cohorts; Days 3, 5, 10 for Cohorts 0.1mg/kg to 10 mg/kg; Days 3, 5, 10, 15 for Cohort 15 mg/kg; Day 15 for Cohort 20 mg/kg)

    Outcome Measure Data

    Analysis Population Description
    Pharmacokinetics (PK) evaluable population included all participants who received any dose of study drug and had at least one postdose PK concentration. Non-compartmental PK analysis was conducted using the data from dose escalation and exploration phases only. The "Number of participants Analyzed" denotes the number of participants evaluated for this outcome measure.
    Arm/Group Title Escalation Cohort (MEDI4736 0.1 mg/kg Q2W) Escalation Cohort (MEDI4736 0.3 mg/kg Q2W) Escalation Cohort (MEDI4736 1 mg/kg Q2W) Escalation Cohort (MEDI4736 3 mg/kg Q2W) Escalation Cohort (MEDI4736 10 mg/kg Q2W) Escalation Cohort (MEDI4736 15 mg/kg Q3W) Exploration Cohort (MEDI4736 20 mg/kg Q4W)
    Arm/Group Description Participants received intravenous (IV) infusion of MEDI4736 (durvalumab) 0.1 mg/kg every 2 weeks (Q2W) in the dose-escalation phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants received IV infusion of MEDI4736 0.3 mg/kg Q2W in the dose-escalation phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation , whichever occurred first Participants received IV infusion of MEDI4736 1 mg/kg Q2W in the dose-escalation phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants received IV infusion of MEDI4736 3 mg/kg Q2W in the dose-escalation phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation , whichever occurred first. Participants received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-escalation phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants received IV infusion of MEDI4736 15 mg/kg every 3 weeks (Q3W) in the dose-escalation phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants received IV infusion of MEDI4736 20 mg/kg every 4 weeks (Q4W) in the dose-exploration phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.
    Measure Participants 4 4 3 3 5 7 18
    Geometric Mean (Geometric Coefficient of Variation) [Day*µg/mL]
    5.144
    (45.1)
    25.063
    (65.5)
    130.546
    (20.1)
    399.863
    (21.7)
    1780.152
    (39.1)
    2943.770
    (36.3)
    4501.888
    (23.1)
    10. Secondary Outcome
    Title Maximum Serum Concentration (Cmax) of MEDI4736 After the First Dose in the Dose-escalation and Dose-exploration Phase
    Description The Cmax of MEDI4736 is reported.
    Time Frame After the first dose between Day 0 and Day 15 (Day 1 [pre and post dose] and predose of Dose 2 for all cohorts; Days 3, 5, 10 for Cohorts 0.1mg/kg to 10 mg/kg; Days 3, 5, 10, 15 for Cohort 15 mg/kg; Day 15 for Cohort 20 mg/kg)

    Outcome Measure Data

    Analysis Population Description
    The PK evaluable population included all participants who received any dose of study drug and had at least one postdose PK concentration. Non-compartmental PK analysis was conducted using the data from dose escalation and exploration phases only. The "Number of participants Analyzed" denotes the number of participants evaluated for this outcome measure.
    Arm/Group Title Escalation Cohort (MEDI4736 0.1 mg/kg Q2W) Escalation Cohort (MEDI4736 0.3 mg/kg Q2W) Escalation Cohort (MEDI4736 1 mg/kg Q2W) Escalation Cohort (MEDI4736 3 mg/kg Q2W) Escalation Cohort (MEDI4736 10 mg/kg Q2W) Escalation Cohort (MEDI4736 15 mg/kg Q3W) Exploration Cohort (MEDI4736 20 mg/kg Q4W)
    Arm/Group Description Participants received intravenous (IV) infusion of MEDI4736 (durvalumab) 0.1 mg/kg every 2 weeks (Q2W) in the dose-escalation phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants received IV infusion of MEDI4736 0.3 mg/kg Q2W in the dose-escalation phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation , whichever occurred first Participants received IV infusion of MEDI4736 1 mg/kg Q2W in the dose-escalation phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants received IV infusion of MEDI4736 3 mg/kg Q2W in the dose-escalation phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation , whichever occurred first. Participants received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-escalation phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants received IV infusion of MEDI4736 15 mg/kg every 3 weeks (Q3W) in the dose-escalation phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants received IV infusion of MEDI4736 20 mg/kg every 4 weeks (Q4W) in the dose-exploration phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.
    Measure Participants 4 4 3 3 5 7 18
    Geometric Mean (Geometric Coefficient of Variation) [µg/mL]
    2.780
    (22.1)
    7.969
    (23.0)
    22.773
    (11.3)
    70.807
    (17.0)
    293.540
    (23.4)
    427.085
    (25.5)
    416.051
    (23.9)
    11. Secondary Outcome
    Title Number of Participants With Positive Anti-drug Antibodies (ADA) to MEDI4736 in the Dose-escalation, Dose-exploration Phase, and Dose-expansion Phase.
    Description Number of participants with positive ADA titer to MEDI4736 are reported. Treatment-boosted ADA is defined as baseline positive ADA titer that was boosted to a 4-fold or higher level following drug administration; persistent positive is defined as positive at >= 2 post-baseline assessments (with >= 16 weeks between first and last positive) or positive at last post-baseline assessment; and transient positive is defined as having at least one post-baseline ADA-positive assessment and not fulfilling the condition of persistent positive.
    Time Frame Escalation: Day1 of Dose(D)1 & D3, even numbered doses after D4; Exploration: Day1 of D1 & D2, even numbered doses after D2; Expansion: Day1 of D1, every 12 weeks since D3; all phases: till EOT, 30 days and 3 and 6 months post last dose (~5.25 years)

    Outcome Measure Data

    Analysis Population Description
    The ADA evaluable population included all participants who received any dose of study drug, had non-missing baseline (before Day 1) ADA, and at least one non-missing post-baseline ADA results. The "Number of participants Analyzed" denotes the number of participants evaluated for this outcome measure.
    Arm/Group Title Total Escalation/Exploration Cohort Expansion SCCHN Cohort (MEDI4736 10 mg/kg Q2W) Expansion Non-SCCHN HPV Positive Cohort (MEDI4736 10 mg/kg Q2W) Expansion NSCLC Cohort (MEDI4736 10 mg/kg Q2W) Expansion HCC Total Cohort (MEDI4736 10 mg/kg Q2W) Expansion ACM Cohort (MEDI4736 10 mg/kg Q2W) Expansion UM Cohort (MEDI4736 10 mg/kg Q2W) Expansion GEC Cohort (MEDI4736 10 mg/kg Q2W) Expansion TNBC Cohort (MEDI4736 10 mg/kg Q2W) Expansion PAC Cohort (MEDI4736 10 mg/kg Q2W) Expansion UC Cohort (MEDI4736 10 mg/kg Q2W) Expansion GBM Cohort (MEDI4736 10 mg/kg Q2W) Expansion OC Cohort (MEDI4736 10 mg/kg Q2W) Expansion STS Cohort (MEDI4736 10 mg/kg Q2W) Expansion SCLC Cohort (MEDI4736 10 mg/kg Q2W) Expansion MSI-high Cancer Cohort (MEDI4736 10 mg/kg Q2W) Expansion NPC Cohort (MEDI4736 10 mg/kg Q2W)
    Arm/Group Description Participants received IV infusion of MEDI4736 0.1 mg/kg, 0.3 mg/kg, 1 mg/kg, 3 mg/kg, and 10 mg/kg Q2W, and 15 mg/kg Q3W in the dose-escalation phase; and 20 mg/kg every 4 weeks (Q4W) in the dose-exploration phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with squamous cell carcinoma of the head and neck (SCCHN) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with non-SCCHN human papilloma virus positive (Non-SCCHN HPV+) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with non-small-cell lung cancer (NSCLC) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with hepatocellular carcinoma (HCC Total) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with advance cutaneous melanoma (ACM) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with uveal melanoma (UM) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with gastroesophageal cancer (GEC) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with triple-negative breast cancer (TNBC) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with pancreatic adenocarcinoma (PAC) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with urothelial carcinoma (UC) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with glioblastoma multiforme (GBM) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose- expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with ovarian cancer (OC) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with soft- tissue sarcoma (STS) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with small-cell lung cancer (SCLC) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with microsatellite instability (MSI)-high cancer received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with nasopharyngeal carcinoma (NPC) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose- expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.
    Measure Participants 45 56 17 257 37 17 21 38 33 26 148 17 41 19 15 58 6
    Positive post-baseline
    4
    100%
    1
    25%
    0
    0%
    6
    200%
    0
    0%
    0
    0%
    1
    4.8%
    0
    0%
    1
    4.5%
    0
    0%
    7
    17.5%
    0
    0%
    2
    8.3%
    1
    2%
    0
    0%
    2
    6.5%
    0
    0%
    Treatment-boosted
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    2.5%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Persistent positive
    2
    50%
    1
    25%
    0
    0%
    4
    133.3%
    1
    16.7%
    0
    0%
    1
    4.8%
    0
    0%
    1
    4.5%
    1
    0.3%
    5
    12.5%
    0
    0%
    0
    0%
    1
    2%
    0
    0%
    1
    3.2%
    0
    0%
    Transient positive
    2
    50%
    0
    0%
    0
    0%
    2
    66.7%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    3
    7.5%
    0
    0%
    2
    8.3%
    0
    0%
    0
    0%
    1
    3.2%
    0
    0%
    12. Secondary Outcome
    Title Number of Participants With Best Overall Response (BOR) Assessed by BICR in NSCLC and SCCHN Cohort in the Dose-expansion Phase
    Description The BOR assessed by BICR based on RECIST v1.1 in NSCLC and SCCHN cohorts is reported. The BOR includes CR, PR, stable disease (SD), progressive disease (PD), and non-evaluable (NE). The CR is defined as disappearance of all target and non-target lesions and no new lesions. The PR is defined as >= 30% decrease in the sum of diameters of target lesions (compared to baseline) and no new nontarget lesion. The PD is defined at least 20% increase in the sum of diameters of target lesions (compared to baseline) and/or new lesion. The SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression. The NE is defined as either when no or only a subset of lesion measurements are made at an assessment.
    Time Frame From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)

    Outcome Measure Data

    Analysis Population Description
    Participants in FAS population with NSCLC and SCCHN were analyzed. FAS population included all participants who received any dose of study drug, had measurable disease at baseline (Day 1) per BICR and were followed for at least 24 weeks by 16Oct2017.
    Arm/Group Title Expansion SCCHN Cohort (MEDI4736 10 mg/kg Q2W) Expansion NSCLC Cohort (MEDI4736 10 mg/kg Q2W)
    Arm/Group Description Participants with SCCHN received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with NSCLC received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.
    Measure Participants 55 275
    CR
    0
    0%
    3
    75%
    PR
    4
    100%
    39
    975%
    SD
    10
    250%
    80
    2000%
    PD
    31
    775%
    110
    2750%
    NE
    10
    250%
    43
    1075%
    13. Secondary Outcome
    Title Number of Participants With BOR Assessed by Investigator in the Dose-escalation, Dose-exploration, and Dose-expansion Phase
    Description The BOR assessed by investigator based on RECIST v1.1 is reported. The BOR includes CR, PR, SD, PD, and NE. The CR is defined as disappearance of all target and non-target lesions and no new lesions. The PR is defined as >= 30% decrease in the sum of diameters of target lesions (compared to baseline) and no new nontarget lesion. The PD is defined at least 20% increase in the sum of diameters of target lesions (compared to baseline) and/or new lesion. The SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression. The NE is defined as either when no or only a subset of lesion measurements are made at an assessment.
    Time Frame From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)

    Outcome Measure Data

    Analysis Population Description
    As-treated population included all participants who received any dose of study drug. The "Number of participants Analyzed" denotes the number of participants evaluated for this outcome measure. One participant from non-SCCHN HPV positive cohort had non-evaluable disease at baseline.
    Arm/Group Title Total Escalation/Exploration Cohort Expansion SCCHN Cohort (MEDI4736 10 mg/kg Q2W) Expansion Non-SCCHN HPV Positive Cohort (MEDI4736 10 mg/kg Q2W) Expansion NSCLC Cohort (MEDI4736 10 mg/kg Q2W) Expansion HCC Total Cohort (MEDI4736 10 mg/kg Q2W) Expansion ACM Cohort (MEDI4736 10 mg/kg Q2W) Expansion UM Cohort (MEDI4736 10 mg/kg Q2W) Expansion GEC Cohort (MEDI4736 10 mg/kg Q2W) Expansion TNBC Cohort (MEDI4736 10 mg/kg Q2W) Expansion PAC Cohort (MEDI4736 10 mg/kg Q2W) Expansion UC Cohort (MEDI4736 10 mg/kg Q2W) Expansion GBM Cohort (MEDI4736 10 mg/kg Q2W) Expansion OC Cohort (MEDI4736 10 mg/kg Q2W) Expansion STS Cohort (MEDI4736 10 mg/kg Q2W) Expansion SCLC Cohort (MEDI4736 10 mg/kg Q2W) Expansion MSI-high Cancer Cohort (MEDI4736 10 mg/kg Q2W) Expansion NPC Cohort (MEDI4736 10 mg/kg Q2W)
    Arm/Group Description Participants received IV infusion of MEDI4736 0.1 mg/kg, 0.3 mg/kg, 1 mg/kg, 3 mg/kg, and 10 mg/kg Q2W, and 15 mg/kg Q3W in the dose-escalation phase; and 20 mg/kg Q4W in the dose-exploration phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with squamous cell carcinoma of the head and neck (SCCHN) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with non-SCCHN human papilloma virus positive (Non-SCCHN HPV+) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with non-small-cell lung cancer (NSCLC) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with hepatocellular carcinoma (HCC Total) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with advance cutaneous melanoma (ACM) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with uveal melanoma (UM) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with gastroesophageal cancer (GEC) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with triple-negative breast cancer (TNBC) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with pancreatic adenocarcinoma (PAC) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with urothelial carcinoma (UC) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with glioblastoma multiforme (GBM) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose- expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with ovarian cancer (OC) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with soft- tissue sarcoma (STS) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with small-cell lung cancer (SCLC) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with microsatellite instability (MSI)-high cancer received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with nasopharyngeal carcinoma (NPC) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose- expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.
    Measure Participants 48 62 22 302 40 21 24 51 40 31 201 20 47 20 21 62 10
    CR
    1
    25%
    1
    25%
    1
    33.3%
    5
    166.7%
    0
    0%
    1
    14.3%
    0
    0%
    1
    1.6%
    0
    0%
    0
    0%
    18
    45%
    0
    0%
    1
    4.2%
    0
    0%
    0
    0%
    3
    9.7%
    0
    0%
    PR
    4
    100%
    6
    150%
    2
    66.7%
    49
    1633.3%
    4
    66.7%
    2
    28.6%
    1
    4.8%
    1
    1.6%
    1
    4.5%
    1
    0.3%
    24
    60%
    0
    0%
    2
    8.3%
    2
    3.9%
    2
    5%
    12
    38.7%
    3
    1.5%
    SD
    18
    450%
    14
    350%
    7
    233.3%
    102
    3400%
    22
    366.7%
    9
    128.6%
    8
    38.1%
    17
    27.4%
    8
    36.4%
    6
    2%
    45
    112.5%
    5
    23.8%
    18
    75%
    8
    15.7%
    4
    10%
    27
    87.1%
    2
    1%
    PD
    18
    450%
    33
    825%
    9
    300%
    103
    3433.3%
    12
    200%
    5
    71.4%
    12
    57.1%
    21
    33.9%
    25
    113.6%
    17
    5.6%
    81
    202.5%
    14
    66.7%
    22
    91.7%
    8
    15.7%
    9
    22.5%
    15
    48.4%
    3
    1.5%
    NE
    7
    175%
    8
    200%
    2
    66.7%
    43
    1433.3%
    2
    33.3%
    4
    57.1%
    3
    14.3%
    11
    17.7%
    6
    27.3%
    7
    2.3%
    33
    82.5%
    1
    4.8%
    4
    16.7%
    2
    3.9%
    6
    15%
    5
    16.1%
    2
    1%
    Not applicable
    0
    0%
    0
    0%
    1
    33.3%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    14. Secondary Outcome
    Title Duration of Response (DoR) Assessed by BICR in NSCLC and SCCHN Cohort in the Dose-expansion Phase
    Description The DoR assessed by BICR in NSCLC and SCCHN cohorts is reported. The DoR is defined as the duration from the first documentation of objective response (OR) (confirmed CR or confirmed PR) to the first documented disease progression based on RECIST v1.1 or death due to any cause, whichever occurred first. A confirmed CR is defined as two CRs (disappearance of all target and non-target lesions and no new lesions) that were separated by at least 28 days with no evidence of progression in-between. A confirmed PR is defined as two PRs (>= 30% decrease in the sum of diameters of target lesions compared to baseline and no new non-target lesion) or an un-confirmed PR and an un-confirmed CR that were separated by at least 4 weeks with no evidence of progression in-between. The DoR was estimated using Kaplan-Meier method.
    Time Frame From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)

    Outcome Measure Data

    Analysis Population Description
    Participants in FAS population with NSCLC and SCCHN were analyzed. FAS population included all participants who received any dose of study drug, had measurable disease at baseline (Day 1) per BICR and were followed for at least 24 weeks by 16Oct2017. The DoR was analyzed for those participants who achieved OR.
    Arm/Group Title Expansion SCCHN Cohort (MEDI4736 10 mg/kg Q2W) Expansion NSCLC Cohort (MEDI4736 10 mg/kg Q2W)
    Arm/Group Description Participants with squamous SCCHN received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with NSCLC received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.
    Measure Participants 4 42
    Median (95% Confidence Interval) [Months]
    12.37
    17.74
    15. Secondary Outcome
    Title DoR Assessed by Investigator in the Dose-expansion Phase
    Description The DoR in participants assessed by the investigator is reported. The DoR is defined as the duration from the first documentation of OR (confirmed CR or confirmed PR) to the first documented disease progression based on RECIST v1.1 or death due to any cause, whichever occurred first. A confirmed CR is defined as two CRs (disappearance of all target and non-target lesions and no new lesions) that were separated by at least 28 days with no evidence of progression in-between. A confirmed PR is defined as two PRs (>= 30% decrease in the sum of diameters of target lesions compared to baseline and no new non-target lesion) or an un-confirmed PR and an un-confirmed CR that were separated by at least 4 weeks with no evidence of progression in-between. The DoR was estimated using Kaplan-Meier method.
    Time Frame From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)

    Outcome Measure Data

    Analysis Population Description
    As-treated population included all participants who received any dose of study drug. The DoR was analyzed for those participants who achieved OR.
    Arm/Group Title Expansion SCCHN Cohort (MEDI4736 10 mg/kg Q2W) Expansion Non-SCCHN HPV Positive Cohort (MEDI4736 10 mg/kg Q2W) Expansion NSCLC Cohort (MEDI4736 10 mg/kg Q2W) Expansion HCC Total Cohort (MEDI4736 10 mg/kg Q2W) Expansion ACM Cohort (MEDI4736 10 mg/kg Q2W) Expansion UM Cohort (MEDI4736 10 mg/kg Q2W) Expansion GEC Cohort (MEDI4736 10 mg/kg Q2W) Expansion TNBC Cohort (MEDI4736 10 mg/kg Q2W) Expansion PAC Cohort (MEDI4736 10 mg/kg Q2W) Expansion UC Cohort (MEDI4736 10 mg/kg Q2W) Expansion GBM Cohort (MEDI4736 10 mg/kg Q2W) Expansion OC Cohort (MEDI4736 10 mg/kg Q2W) Expansion STS Cohort (MEDI4736 10 mg/kg Q2W) Expansion SCLC Cohort (MEDI4736 10 mg/kg Q2W) Expansion MSI-high Cancer Cohort (MEDI4736 10 mg/kg Q2W) Expansion NPC Cohort (MEDI4736 10 mg/kg Q2W)
    Arm/Group Description Participants with squamous cell carcinoma of the head and neck (SCCHN) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with non-SCCHN human papilloma virus positive (Non-SCCHN HPV+) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with non-small-cell lung cancer (NSCLC) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with hepatocellular carcinoma (HCC Total) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with advance cutaneous melanoma (ACM) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with uveal melanoma (UM) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with gastroesophageal cancer (GEC) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with triple-negative breast cancer (TNBC) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with pancreatic adenocarcinoma (PAC) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with urothelial carcinoma (UC) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with glioblastoma multiforme (GBM) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose- expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with ovarian cancer (OC) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with soft- tissue sarcoma (STS) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with small-cell lung cancer (SCLC) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with microsatellite instability (MSI)-high cancer received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with nasopharyngeal carcinoma (NPC) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose- expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.
    Measure Participants 7 3 54 4 3 1 2 1 1 42 0 3 2 2 15 3
    Median (95% Confidence Interval) [Months]
    19.71
    14.75
    9.95
    16.20
    NA
    9.23
    NA
    NA
    5.36
    NA
    24.87
    7.92
    23.51
    26.91
    8.64
    16. Secondary Outcome
    Title Disease Control Rate (DCR) Assessed by BICR in NSCLC and SCCHN Cohort in the Dose-expansion Phase
    Description Percentage of participants with disease control assessed by BICR in NSCLC and SCCHN cohorts is reported. Disease control is defined as a BOR of confirmed CR, confirmed PR, or SD based on RECIST v1.1. A confirmed CR is defined as two CRs (disappearance of all target and non-target lesions and no new lesions) that were separated by at least 28 days with no evidence of progression in-between. A confirmed PR is defined as two PRs (>= 30% decrease in the sum of diameters of target lesions compared to baseline and no new non-target lesion) or an un-confirmed PR and an unconfirmed CR that were separated by at least 28 days with no evidence of progression in-between. The SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression.
    Time Frame From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)

    Outcome Measure Data

    Analysis Population Description
    Participants in FAS population with NSCLC and SCCHN were analyzed. FAS population included all participants who received any dose of study drug, had measurable disease at baseline (Day 1) per BICR and were followed for at least 24 weeks by 16Oct2017.
    Arm/Group Title Expansion SCCHN Cohort (MEDI4736 10 mg/kg Q2W) Expansion NSCLC Cohort (MEDI4736 10 mg/kg Q2W)
    Arm/Group Description Participants with SCCHN received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with NSCLC received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.
    Measure Participants 55 275
    Number (95% Confidence Interval) [Percentage of participants]
    25.5
    637.5%
    44.4
    1110%
    17. Secondary Outcome
    Title DCR Assessed by Investigator in the Dose-expansion Phase
    Description Percentage of participants with disease control assessed by the investigator is reported. Disease control is defined as a BOR of confirmed CR, confirmed PR, or SD based on RECIST v1.1. A confirmed CR is defined as two CRs (disappearance of all target and non-target lesions and no new lesions) that were separated by at least 28 days with no evidence of progression in-between. A confirmed PR is defined as two PRs (>= 30% decrease in the sum of diameters of target lesions compared to baseline and no new non-target lesion) or an un-confirmed PR and an unconfirmed CR that were separated by at least 28 days with no evidence of progression in-between. The SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression.
    Time Frame From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)

    Outcome Measure Data

    Analysis Population Description
    As-treated population included all participants who received any dose of study drug.
    Arm/Group Title Expansion SCCHN Cohort (MEDI4736 10 mg/kg Q2W) Expansion Non-SCCHN HPV Positive Cohort (MEDI4736 10 mg/kg Q2W) Expansion NSCLC Cohort (MEDI4736 10 mg/kg Q2W) Expansion HCC Total Cohort (MEDI4736 10 mg/kg Q2W) Expansion ACM Cohort (MEDI4736 10 mg/kg Q2W) Expansion UM Cohort (MEDI4736 10 mg/kg Q2W) Expansion GEC Cohort (MEDI4736 10 mg/kg Q2W) Expansion TNBC Cohort (MEDI4736 10 mg/kg Q2W) Expansion PAC Cohort (MEDI4736 10 mg/kg Q2W) Expansion UC Cohort (MEDI4736 10 mg/kg Q2W) Expansion GBM Cohort (MEDI4736 10 mg/kg Q2W) Expansion OC Cohort (MEDI4736 10 mg/kg Q2W) Expansion STS Cohort (MEDI4736 10 mg/kg Q2W) Expansion SCLC Cohort (MEDI4736 10 mg/kg Q2W) Expansion MSI-high Cancer Cohort (MEDI4736 10 mg/kg Q2W) Expansion NPC Cohort (MEDI4736 10 mg/kg Q2W)
    Arm/Group Description Participants with squamous cell carcinoma of the head and neck (SCCHN) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with non-SCCHN human papilloma virus positive (Non-SCCHN HPV+) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with non-small-cell lung cancer (NSCLC) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with hepatocellular carcinoma (HCC Total) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with advance cutaneous melanoma (ACM) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with uveal melanoma (UM) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with gastroesophageal cancer (GEC) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with triple-negative breast cancer (TNBC) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with pancreatic adenocarcinoma (PAC) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with urothelial carcinoma (UC) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with glioblastoma multiforme (GBM) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose- expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with ovarian cancer (OC) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with soft- tissue sarcoma (STS) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with small-cell lung cancer (SCLC) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with microsatellite instability (MSI)-high cancer received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with nasopharyngeal carcinoma (NPC) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose- expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.
    Measure Participants 62 22 302 40 21 24 51 40 31 201 20 47 20 21 62 10
    Number (95% Confidence Interval) [Percentage of participants]
    33.9
    847.5%
    45.5
    1137.5%
    51.7
    1723.3%
    65.0
    2166.7%
    57.1
    951.7%
    37.5
    535.7%
    37.3
    177.6%
    22.5
    36.3%
    22.6
    102.7%
    43.3
    14.2%
    0
    0%
    44.7
    212.9%
    50.0
    208.3%
    28.6
    56.1%
    67.7
    169.3%
    50.0
    161.3%
    18. Secondary Outcome
    Title Progression-free Survival (PFS) Assessed by BICR in NSCLC Cohort in the Dose-expansion Phase
    Description The PFS assessed by BICR in NSCLC cohort is reported. The PFS is defined as the time from the start of study treatment until the first documentation of disease progression based on RECIST v1.1 or death due to any cause, whichever occurred first. The PD is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study; the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. The PFS was estimated using Kaplan-Meier method.
    Time Frame From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)

    Outcome Measure Data

    Analysis Population Description
    Participants in As-treated population with NSCLC were analyzed. As-treated population included all participants who received any dose of study drug.
    Arm/Group Title Expansion NSCLC Cohort (MEDI4736 10 mg/kg Q2W)
    Arm/Group Description Participants with NSCLC received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.
    Measure Participants 304
    Median (95% Confidence Interval) [Percentage of participants]
    2.1
    52.5%
    19. Secondary Outcome
    Title PFS Assessed by BICR in SCCHN Cohort in the Dose-expansion Phase
    Description The PFS assessed by BICR in SCCHN cohort is reported. The PFS is defined as the time from the start of study treatment until the first documentation of disease progression based on RECIST v1.1 or death due to any cause, whichever occurred first. The PD is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study; the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. The PFS was estimated using Kaplan-Meier method.
    Time Frame From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)

    Outcome Measure Data

    Analysis Population Description
    Participants in FAS population with SCCHN were analyzed. FAS population included all participants who received any dose of study drug, had measurable disease at baseline (Day 1) per BICR and were followed for at least 24 weeks by 16Oct2017.
    Arm/Group Title Expansion SCCHN Cohort (MEDI4736 10 mg/kg Q2W)
    Arm/Group Description Participants with SCCHN received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.
    Measure Participants 62
    Median (95% Confidence Interval) [Percentage of participants]
    1.4
    35%
    20. Secondary Outcome
    Title PFS Assessed by Investigator in the Dose-expansion Phase
    Description The PFS assessed by the investigator is reported. The PFS is defined as the time from the start of study treatment until the first documentation of disease progression based on RECIST v1.1 or death due to any cause, whichever occurred first. The PD is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study; the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. The PFS was estimated using Kaplan-Meier method.
    Time Frame From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)

    Outcome Measure Data

    Analysis Population Description
    As-treated population included all participants who received any dose of study drug. The "Number of participants Analyzed" denotes the number of participants evaluated for this outcome measure.
    Arm/Group Title Expansion SCCHN Cohort (MEDI4736 10 mg/kg Q2W) Expansion Non-SCCHN HPV Positive Cohort (MEDI4736 10 mg/kg Q2W) Expansion NSCLC Cohort (MEDI4736 10 mg/kg Q2W) Expansion HCC Total Cohort (MEDI4736 10 mg/kg Q2W) Expansion ACM Cohort (MEDI4736 10 mg/kg Q2W) Expansion UM Cohort (MEDI4736 10 mg/kg Q2W) Expansion GEC Cohort (MEDI4736 10 mg/kg Q2W) Expansion TNBC Cohort (MEDI4736 10 mg/kg Q2W) Expansion PAC Cohort (MEDI4736 10 mg/kg Q2W) Expansion UC Cohort (MEDI4736 10 mg/kg Q2W) Expansion GBM Cohort (MEDI4736 10 mg/kg Q2W) Expansion OC Cohort (MEDI4736 10 mg/kg Q2W) Expansion STS Cohort (MEDI4736 10 mg/kg Q2W) Expansion SCLC Cohort (MEDI4736 10 mg/kg Q2W) Expansion MSI-high Cancer Cohort (MEDI4736 10 mg/kg Q2W) Expansion NPC Cohort (MEDI4736 10 mg/kg Q2W)
    Arm/Group Description Participants with squamous cell carcinoma of the head and neck (SCCHN) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with non-SCCHN human papilloma virus positive (Non-SCCHN HPV+) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with non-small-cell lung cancer (NSCLC) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with hepatocellular carcinoma (HCC Total) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with advance cutaneous melanoma (ACM) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with uveal melanoma (UM) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with gastroesophageal cancer (GEC) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with triple-negative breast cancer (TNBC) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with pancreatic adenocarcinoma (PAC) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with urothelial carcinoma (UC) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with glioblastoma multiforme (GBM) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose- expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with ovarian cancer (OC) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with soft- tissue sarcoma (STS) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with small-cell lung cancer (SCLC) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with microsatellite instability (MSI)-high cancer received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with nasopharyngeal carcinoma (NPC) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose- expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.
    Measure Participants 62 22 302 40 21 24 51 40 31 201 20 47 20 21 62 10
    Median (95% Confidence Interval) [Months]
    1.4
    1.5
    2.6
    2.7
    2.8
    1.4
    1.4
    1.3
    1.5
    1.8
    1.4
    1.8
    2.6
    1.5
    5.4
    2.2
    21. Secondary Outcome
    Title OS in the Dose-Expansion Phase
    Description OS is defined as the time from the start of study treatment until death due to any cause. The OS was estimated using Kaplan-Meier method.
    Time Frame From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)

    Outcome Measure Data

    Analysis Population Description
    As-treated population included all participants who received any dose of study drug. The "Number of Participants Analyzed" denotes the number of participants evaluated for this outcome measure.
    Arm/Group Title Expansion SCCHN Cohort (MEDI4736 10 mg/kg Q2W) Expansion Non-SCCHN HPV Positive Cohort (MEDI4736 10 mg/kg Q2W) Expansion NSCLC Cohort (MEDI4736 10 mg/kg Q2W) Expansion HCC Total Cohort (MEDI4736 10 mg/kg Q2W) Expansion ACM Cohort (MEDI4736 10 mg/kg Q2W) Expansion UM Cohort (MEDI4736 10 mg/kg Q2W) Expansion GEC Cohort (MEDI4736 10 mg/kg Q2W) Expansion TNBC Cohort (MEDI4736 10 mg/kg Q2W) Expansion PAC Cohort (MEDI4736 10 mg/kg Q2W) Expansion UC Cohort (MEDI4736 10 mg/kg Q2W) Expansion GBM Cohort (MEDI4736 10 mg/kg Q2W) Expansion OC Cohort (MEDI4736 10 mg/kg Q2W) Expansion STS Cohort (MEDI4736 10 mg/kg Q2W) Expansion SCLC Cohort (MEDI4736 10 mg/kg Q2W) Expansion MSI-high Cancer Cohort (MEDI4736 10 mg/kg Q2W) Expansion NPC Cohort (MEDI4736 10 mg/kg Q2W)
    Arm/Group Description Participants with squamous cell carcinoma of the head and neck (SCCHN) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with non-SCCHN human papilloma virus positive (Non-SCCHN HPV+) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with non-small-cell lung cancer (NSCLC) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with hepatocellular carcinoma (HCC Total) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with advance cutaneous melanoma (ACM) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with uveal melanoma (UM) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with gastroesophageal cancer (GEC) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with triple-negative breast cancer (TNBC) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with pancreatic adenocarcinoma (PAC) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with urothelial carcinoma (UC) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with glioblastoma multiforme (GBM) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose- expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with ovarian cancer (OC) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with soft- tissue sarcoma (STS) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with small-cell lung cancer (SCLC) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with microsatellite instability (MSI)-high cancer received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with nasopharyngeal carcinoma (NPC) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose- expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.
    Measure Participants 62 22 304 40 21 24 51 40 31 201 20 47 20 21 62 10
    Median (95% Confidence Interval) [Months]
    8.4
    11.6
    12.4
    13.2
    NA
    8.4
    4.9
    5.5
    5.7
    10.5
    10.0
    11.1
    15.8
    4.8
    24.1
    16.1
    22. Secondary Outcome
    Title ORR Assessed by BICR in UC Cohort (PD-L1 Low/Negative, Total, and PD-L1 High) in the Dose-expansion Phase
    Description The ORR assessed by BICR in UC cohort is reported. The ORR is defined as confirmed CR or confirmed PR based on RECIST v1.1. The CR is defined as disappearance of all target and non-target lesions and no new lesions. A confirmed CR is defined as two CRs that were separated by at least 28 days with no evidence of progression in-between. The PR is defined as >= 30% decrease in the sum of diameters of target lesions (compared to baseline) and no new nontarget lesion. A confirmed PR is defined as two PRs or an un-confirmed PR and an un-confirmed CR that were separated by at least 4 weeks with no evidence of progression in-between.
    Time Frame From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)

    Outcome Measure Data

    Analysis Population Description
    The UC cohort participants with PD-L1 status as low/negative (<25% tumor cell membrane and <25% immune cell staining), total (PD-L1 high, PD-L1 low/negative, and PD-L1 unknown), and high (>= 25% tumor cell membrane or >=25% immune cell staining) included in the FAS population were analyzed. FAS population included all participnats who received any dose of study drug, had measurable disease at baseline (Day 1) per BICR and were followed for at least 24 weeks by 16Oct2017.
    Arm/Group Title Expansion UC PD-L1 Low/Negative Cohort Expansion UC Total Cohort Expansion UC PD-L1 High Cohort
    Arm/Group Description Participants with UC (PD-L1 status low/Negative) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with UC (Total PD-L1 status - high, low/Negative, and unknown) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with UC (PD-L1 status high) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.
    Measure Participants 85 199 101
    Number (95% Confidence Interval) [Percentage of participants]
    5.9
    147.5%
    17.6
    440%
    27.7
    923.3%
    23. Secondary Outcome
    Title ORR Assessed by Investigator in UC Cohort (PD-L1 Low/Negative, Total, and PD-L1 High) in the Dose-expansion Phase
    Description The ORR assessed by the investigator in UC cohort is reported. The ORR is defined as confirmed CR or confirmed PR based on RECIST v1.1. The CR is defined as disappearance of all target and non-target lesions and no new lesions. A confirmed CR is defined as two CRs that were separated by at least 28 days with no evidence of progression in-between. The PR is defined as >= 30% decrease in the sum of diameters of target lesions (compared to baseline) and no new nontarget lesion. A confirmed PR is defined as two PRs or an un-confirmed PR and an un-confirmed CR that were separated by at least 4 weeks with no evidence of progression in-between.
    Time Frame From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)

    Outcome Measure Data

    Analysis Population Description
    The UC cohort participants with PD-L1 status as low/negative (<25% tumor cell membrane and <25% immune cell staining), total (PD-L1 high, PD-L1 low/negative, and PD-L1 unknown), and high (>= 25% tumor cell membrane or >=25% immune cell staining) included in the As-treated population were analyzed. As-treated population included all participants who received any dose of study drug.
    Arm/Group Title Expansion UC PD-L1 Low/Negative Cohort Expansion UC Total Cohort Expansion UC PD-L1 High Cohort
    Arm/Group Description Participants with UC (PD-L1 status low/Negative) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with UC (Total PD-L1 status - high, low/Negative, and unknown) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with UC (PD-L1 status high) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.
    Measure Participants 86 201 102
    Number (95% Confidence Interval) [Percentage of participants]
    7.0
    175%
    20.9
    522.5%
    33.3
    1110%
    24. Secondary Outcome
    Title DoR Assessed by BICR in UC Cohort (PD-L1 Low/Negative, Total, and PD-L1 High) in the Dose-expansion Phase
    Description The DoR assessed by BICR in UC cohort is reported. The DoR is defined as the duration from the first documentation of OR (confirmed CR or confirmed PR) to the first documented disease progression based on RECIST v1.1 or death due to any cause, whichever occurred first. A confirmed CR is defined as two CRs (disappearance of all target and non-target lesions and no new lesions) that were separated by at least 28 days with no evidence of progression in-between. A confirmed PR is defined as two PRs (>= 30% decrease in the sum of diameters of target lesions compared to baseline and no new non-target lesion) or an un-confirmed PR and an un-confirmed CR that were separated by at least 4 weeks with no evidence of progression in-between. The DoR was estimated using Kaplan-Meier method.
    Time Frame From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)

    Outcome Measure Data

    Analysis Population Description
    The UC cohort participants with PD-L1 status low/negative (<25% tumor cell membrane and <25% immune cell staining), total (PD-L1 high, PD-L1 low/negative, and PD-L1 unknown), and high (>= 25% tumor cell membrane or >=25% immune cell staining) included in FAS population (all participants who received any dose of study drug, had measurable disease at baseline (Day 1) per BICR and were followed for at least 24 wks by 16Oct2017) were analyzed. DoR was analyzed for those participants who achieved OR.
    Arm/Group Title Expansion UC PD-L1 Low/Negative Cohort Expansion UC Total Cohort Expansion UC PD-L1 High Cohort
    Arm/Group Description Participants with UC (PD-L1 status low/Negative) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with UC (Total PD-L1 status - high, low/Negative, and unknown) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with UC (PD-L1 status high) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.
    Measure Participants 5 35 28
    Median (95% Confidence Interval) [Months]
    12.25
    NA
    NA
    25. Secondary Outcome
    Title DoR Assessed by Investigator in UC Cohort (PD-L1 Low/Negative, Total, and PD-L1 High) in the Dose-expansion Phase
    Description The DoR assessed by investigator in UC cohort is reported. The DoR is defined as the duration from the first documentation of OR (confirmed CR or confirmed PR) to the first documented disease progression based on RECIST v1.1 or death due to any cause, whichever occurred first. A confirmed CR is defined as two CRs (disappearance of all target and non-target lesions and no new lesions) that were separated by at least 28 days with no evidence of progression in-between. A confirmed PR is defined as two PRs (>= 30% decrease in the sum of diameters of target lesions compared to baseline and no new non-target lesion) or an un-confirmed PR and an un-confirmed CR that were separated by at least 4 weeks with no evidence of progression in-between. The DoR was estimated using Kaplan-Meier method.
    Time Frame From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)

    Outcome Measure Data

    Analysis Population Description
    The UC cohort participants with PD-L1 status as low/negative (<25% tumor cell membrane and <25% immune cell staining), total (PD-L1 high, PD-L1 low/negative, and PD-L1 unknown), and high (>= 25% tumor cell membrane or >=25% immune cell staining) included in the As-treated population were analyzed. As-treated population included all participants who received any dose of study drug. The DoR was analyzed for those participants who achieved OR.
    Arm/Group Title Expansion UC PD-L1 Low/Negative Cohort Expansion UC Total Cohort Expansion UC PD-L1 High Cohort
    Arm/Group Description Participants with UC (PD-L1 status low/Negative) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with UC (Total PD-L1 status - high, low/Negative, and unknown) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with UC (PD-L1 status high) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.
    Measure Participants 6 42 34
    Median (95% Confidence Interval) [Months]
    14.82
    19.71
    NA
    26. Secondary Outcome
    Title DCR Assessed by BICR in UC Cohort (PD-L1 Low/Negative, Total, and PD-L1 High) in the Dose-expansion Phase
    Description Percentage of participants with disease control assessed by BICR in UC cohort is reported. The DCR is defined as a BOR of confirmed CR, confirmed PR, or SD based on RECIST v1.1. A confirmed CR is defined as two CRs (disappearance of all target and non-target lesions and no new lesions) that were separated by at least 28 days with no evidence of progression in-between. A confirmed PR is defined as two PRs (>= 30% decrease in the sum of diameters of target lesions compared to baseline and no new non-target lesion) or an un-confirmed PR and an unconfirmed CR that were separated by at least 28 days with no evidence of progression in-between. The SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression.
    Time Frame From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)

    Outcome Measure Data

    Analysis Population Description
    The UC cohort participants with PD-L1 status as low/negative (<25% tumor cell membrane and <25% immune cell staining), total (PD-L1 high, PD-L1 low/negative, and PD-L1 unknown), and high (>= 25% tumor cell membrane or >=25% immune cell staining) included in the FAS population were analyzed. FAS population included all participants who received any dose of study drug, had measurable disease at baseline (Day 1) per BICR and were followed for at least 24 weeks by 16Oct2017.
    Arm/Group Title Expansion UC PD-L1 Low/Negative Cohort Expansion UC Total Cohort Expansion UC PD-L1 High Cohort
    Arm/Group Description Participants with UC (PD-L1 status low/Negative) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with UC (Total PD-L1 status - high, low/Negative, and unknown) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with UC (PD-L1 status high) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.
    Measure Participants 85 199 101
    Number (95% Confidence Interval) [Percentage of participants]
    21.2
    530%
    35.2
    880%
    43.6
    1453.3%
    27. Secondary Outcome
    Title DCR Assessed by Investigator in UC Cohort (PD-L1 Low/Negative, Total, and PD-L1 High) in the Dose-expansion Phase
    Description Percentage of participants with disease control assessed by investigator in UC cohort is reported. Disease control is defined as a best overall response of confirmed CR, confirmed PR, or SD based on RECIST v1.1. A confirmed CR is defined as two CRs (disappearance of all target and non-target lesions and no new lesions) that were separated by at least 28 days with no evidence of progression in-between. A confirmed PR is defined as two PRs (>= 30% decrease in the sum of diameters of target lesions compared to baseline and no new non-target lesion) or an un-confirmed PR and an unconfirmed CR that were separated by at least 28 days with no evidence of progression in-between. The SD is defined as neither sufficient shrinkage to qualify for PR not sufficient increase to qualify for disease progression.
    Time Frame From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)

    Outcome Measure Data

    Analysis Population Description
    The UC cohort participants with PD-L1 status as low/negative (<25% tumor cell membrane and <25% immune cell staining), total (PD-L1 high, PD-L1 low/negative, and PD-L1 unknown), and high (>= 25% tumor cell membrane or >=25% immune cell staining) included in the As-treated population were analyzed. As-treated population included all participants who received any dose of study drug.
    Arm/Group Title Expansion UC PD-L1 Low/Negative Cohort Expansion UC Total Cohort Expansion UC PD-L1 High Cohort
    Arm/Group Description Participants with UC (PD-L1 status low/Negative) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with UC (Total PD-L1 status - high, low/Negative, and unknown) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with UC (PD-L1 status high) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.
    Measure Participants 86 201 102
    Number (95% Confidence Interval) [Percentage of participants]
    30.2
    755%
    43.3
    1082.5%
    53.9
    1796.7%
    28. Secondary Outcome
    Title PFS Assessed by BICR in UC Cohort (PD-L1 Low/Negative, Total, and PD-L1 High) in the Dose-expansion Phase
    Description The PFS assessed by BICR in UC cohort is reported. The PFS is defined as the time from the start of study treatment until the first documentation of disease progression based on RECIST v1.1 or death due to any cause, whichever occurred first. The PD is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study; the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. The PFS was estimated using Kaplan-Meier method.
    Time Frame From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)

    Outcome Measure Data

    Analysis Population Description
    The UC cohort participants with PD-L1 status as low/negative (<25% tumor cell membrane and <25% immune cell staining), total (PD-L1 high, PD-L1 low/negative, and PD-L1 unknown), and high (>= 25% tumor cell membrane or >=25% immune cell staining) included in the As-treated population were analyzed. As-treated population included all participants who received any dose of study drug. The "Number of participants Analyzed" denotes the number of participants evaluated for this outcome measure.
    Arm/Group Title Expansion UC PD-L1 Low/Negative Cohort Expansion UC Total Cohort Expansion UC PD-L1 High Cohort
    Arm/Group Description Participants with UC (PD-L1 status low/Negative) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with UC (Total PD-L1 status - high, low/Negative, and unknown) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with UC (PD-L1 status high) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.
    Measure Participants 86 201 102
    Median (95% Confidence Interval) [Months]
    1.4
    1.5
    1.9
    29. Secondary Outcome
    Title PFS Assessed by Investigator in UC Cohort (PD-L1 Low/Negative, Total, and PD-L1 High) in the Dose-expansion Phase
    Description The PFS assessed by the investigator in UC cohort is reported. The PFS is defined as the time from the start of study treatment until the first documentation of disease progression based on RECIST v1.1 or death due to any cause, whichever occurred first. The PD is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study; the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. The PFS was estimated using Kaplan-Meier method.
    Time Frame From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)

    Outcome Measure Data

    Analysis Population Description
    The UC cohort participants with PD-L1 status as low/negative (<25% tumor cell membrane and <25% immune cell staining), total (PD-L1 high, PD-L1 low/negative, and PD-L1 unknown), and high (>= 25% tumor cell membrane or >=25% immune cell staining) included in the As-treated population were analyzed. As-treated population included all participants who received any dose of study drug. The "Number of participants Analyzed" denotes the number of participants evaluated for this outcome measure.
    Arm/Group Title Expansion UC PD-L1 Low/Negative Cohort Expansion UC Total Cohort Expansion UC PD-L1 High Cohort
    Arm/Group Description Participants with UC (PD-L1 status low/Negative) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with UC (Total PD-L1 status - high, low/Negative, and unknown) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with UC (PD-L1 status high) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.
    Measure Participants 86 201 102
    Median (95% Confidence Interval) [Months]
    1.4
    1.8
    2.8
    30. Secondary Outcome
    Title OS in UC Cohort (PD-L1 Low/Negative, Total, and PD-L1 High) in the Dose-expansion Phase
    Description The OS in UC cohort is reported. The OS is defined as the time from the start of study treatment until death due to any cause. The OS was estimated using Kaplan-Meier method.
    Time Frame From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)

    Outcome Measure Data

    Analysis Population Description
    The UC cohort participants with PD-L1 status as low/negative (<25% tumor cell membrane and <25% immune cell staining), total (PD-L1 high, PD-L1 low/negative, and PD-L1 unknown), and high (>= 25% tumor cell membrane or >=25% immune cell staining) included in the As-treated population were analyzed. As-treated population included all participants who received any dose of study drug. The "Number of Participants Analyzed" denotes the number of participants evaluated for this outcome measure.
    Arm/Group Title Expansion UC PD-L1 Low/Negative Cohort Expansion UC Total Cohort Expansion UC PD-L1 High Cohort
    Arm/Group Description Participants with UC (PD-L1 status low/Negative) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with UC (Total PD-L1 status - high, low/Negative, and unknown) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with UC (PD-L1 status high) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.
    Measure Participants 86 201 102
    Median (95% Confidence Interval) [Months]
    4.8
    10.5
    19.8
    31. Secondary Outcome
    Title Adjusted Comparison of PFS by PD-L1 Status in UC Cohort in the Dose-expansion Phase
    Description The PFS by PD-L1 status in UC cohort is reported. The PFS estimates are adjusted for baseline eastern cooperative oncology (ECOG), smoking status, race, gender, age, previous lines of therapy, and liver metastasis. 95% CIs based on log (-log(survival)). The PFS is defined as the time from the start of study treatment until the first documentation of disease progression based on RECIST v1.1 or death due to any cause, whichever occurred first. The PD is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study; the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. The PFS was estimated using Kaplan-Meier method.
    Time Frame From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)

    Outcome Measure Data

    Analysis Population Description
    The UC cohort participants with PD-L1 status as high (>= 25% tumor cell membrane or >=25% immune cell staining) and low/negative (<25% tumor cell membrane and <25% immune cell staining) included in the As-treated population were analyzed. As-treated population included all participants who received any dose of study drug. The "Number of participants Analyzed" denotes the number of participants evaluated for this outcome measure.
    Arm/Group Title Expansion UC PD-L1 High Cohort Expansion UC PD-L1 Low/Negative Cohort
    Arm/Group Description Participants with UC (PD-L1 status high) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with UC (PD-L1 status low/Negative) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.
    Measure Participants 61 39
    Median (95% Confidence Interval) [Months]
    2.6
    1.5
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Escalation Cohort (MEDI4736 0.1 mg/kg Q2W), Escalation Cohort (MEDI4736 0.3 mg/kg Q2W)
    Comments
    Type of Statistical Test Equivalence
    Comments Other
    Statistical Test of Hypothesis p-Value 0.016
    Comments
    Method Regression, Cox
    Comments
    32. Secondary Outcome
    Title Adjusted Comparison of OS by PD-L1 Status in UC Cohort in the Dose-expansion Phase
    Description The OS by PD-L1 status in UC cohort is reported. The OS estimates are adjusted for baseline ECOG, smoking status, race, gender, age, previous lines of therapy, and liver metastasis. 95% CIs based on log (-log(survival)). The OS is defined as the time from the start of study treatment until death due to any cause. The OS was estimated using Kaplan-Meier method.
    Time Frame From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)

    Outcome Measure Data

    Analysis Population Description
    The UC cohort participants with PD-L1 status as high (>= 25% tumor cell membrane or >=25% immune cell staining) and low/negative (<25% tumor cell membrane and <25% immune cell staining) included in the As-treated population were analyzed. As-treated population included all participants who received any dose of study drug. The "Number of Participants Analyzed" denotes the number of participants evaluated for this outcome measure.
    Arm/Group Title Expansion UC PD-L1 High Cohort Expansion UC PD-L1 Low/Negative Cohort
    Arm/Group Description Participants with UC (PD-L1 status high) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with UC (PD-L1 status low/Negative) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.
    Measure Participants 61 39
    Median (95% Confidence Interval) [Months]
    18.4
    3.4
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Escalation Cohort (MEDI4736 0.1 mg/kg Q2W), Escalation Cohort (MEDI4736 0.3 mg/kg Q2W)
    Comments
    Type of Statistical Test Equivalence
    Comments Other
    Statistical Test of Hypothesis p-Value 0.0046
    Comments
    Method Regression, Cox
    Comments

    Adverse Events

    Time Frame From Day 1 through 90 days after the last dose of study drug (approximately 5.25 years)
    Adverse Event Reporting Description
    Arm/Group Title Escalation Cohort (MEDI4736 0.1 mg/kg Q2W) Escalation Cohort (MEDI4736 0.3 mg/kg Q2W) Escalation Cohort (MEDI4736 1 mg/kg Q2W) Escalation Cohort (MEDI4736 3 mg/kg Q2W) Escalation Cohort (MEDI4736 10 mg/kg Q2W) Escalation Cohort (MEDI4736 15 mg/kg Q3W) Exploration Durvalumab 20 mg/kg (Q4W) Expansion SCCHN Cohort (MEDI4736 10 mg/kg Q2W) Expansion Non-SCCHN HPV Positive Cohort (MEDI4736 10 mg/kg Q2W) Expansion NSCLC Cohort (MEDI4736 10 mg/kg Q2W) Expansion HCC Total Cohort (MEDI4736 10 mg/kg Q2W) Expansion ACM Cohort (MEDI4736 10 mg/kg Q2W) Expansion UM Cohort (MEDI4736 10 mg/kg Q2W) Expansion GEC Cohort (MEDI4736 10 mg/kg Q2W) Expansion TNBC Cohort (MEDI4736 10 mg/kg Q2W) Expansion PAC Cohort (MEDI4736 10 mg/kg Q2W) Expansion UC Cohort (MEDI4736 10 mg/kg Q2W) Expansion GBM Cohort (MEDI4736 10 mg/kg Q2W) Expansion OC Cohort (MEDI4736 10 mg/kg Q2W) Expansion STS Cohort (MEDI4736 10 mg/kg Q2W) Expansion SCLC Cohort (MEDI4736 10 mg/kg Q2W) Expansion MSI-high Cancer Cohort (MEDI4736 10 mg/kg Q2W) Expansion NPC Cohort (MEDI4736 10 mg/kg Q2W)
    Arm/Group Description Participants received intravenous (IV) infusion of MEDI4736 (durvalumab) 0.1 mg/kg every 2 weeks (Q2W) in the dose-escalation phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants received IV infusion of MEDI4736 0.3 mg/kg Q2W in the dose-escalation phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants received IV infusion of MEDI4736 1 mg/kg Q2W in the dose-escalation phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants received IV infusion of MEDI4736 3 mg/kg Q2W in the dose-escalation phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-escalation phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants received IV infusion of MEDI4736 15 mg/kg every 3 weeks (Q3W) in the dose-escalation phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants received IV infusion of MEDI4736 20 mg/kg every 4 weeks (Q4W) in the dose-exploration phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with squamous cell carcinoma of the head and neck (SCCHN) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with non-SCCHN human papilloma virus positive (Non-SCCHN HPV+) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with non-small-cell lung cancer (NSCLC) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with hepatocellular carcinoma (HCC Total) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with advance cutaneous melanoma (ACM) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with uveal melanoma (UM) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with gastroesophageal cancer (GEC) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with triple-negative breast cancer (TNBC) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with pancreatic adenocarcinoma (PAC) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with urothelial carcinoma (UC) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with glioblastoma multiforme (GBM) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose- expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with ovarian cancer (OC) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with soft- tissue sarcoma (STS) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with small-cell lung cancer (SCLC) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with microsatellite instability (MSI)-high cancer received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first. Participants with nasopharyngeal carcinoma (NPC) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose- expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.
    All Cause Mortality
    Escalation Cohort (MEDI4736 0.1 mg/kg Q2W) Escalation Cohort (MEDI4736 0.3 mg/kg Q2W) Escalation Cohort (MEDI4736 1 mg/kg Q2W) Escalation Cohort (MEDI4736 3 mg/kg Q2W) Escalation Cohort (MEDI4736 10 mg/kg Q2W) Escalation Cohort (MEDI4736 15 mg/kg Q3W) Exploration Durvalumab 20 mg/kg (Q4W) Expansion SCCHN Cohort (MEDI4736 10 mg/kg Q2W) Expansion Non-SCCHN HPV Positive Cohort (MEDI4736 10 mg/kg Q2W) Expansion NSCLC Cohort (MEDI4736 10 mg/kg Q2W) Expansion HCC Total Cohort (MEDI4736 10 mg/kg Q2W) Expansion ACM Cohort (MEDI4736 10 mg/kg Q2W) Expansion UM Cohort (MEDI4736 10 mg/kg Q2W) Expansion GEC Cohort (MEDI4736 10 mg/kg Q2W) Expansion TNBC Cohort (MEDI4736 10 mg/kg Q2W) Expansion PAC Cohort (MEDI4736 10 mg/kg Q2W) Expansion UC Cohort (MEDI4736 10 mg/kg Q2W) Expansion GBM Cohort (MEDI4736 10 mg/kg Q2W) Expansion OC Cohort (MEDI4736 10 mg/kg Q2W) Expansion STS Cohort (MEDI4736 10 mg/kg Q2W) Expansion SCLC Cohort (MEDI4736 10 mg/kg Q2W) Expansion MSI-high Cancer Cohort (MEDI4736 10 mg/kg Q2W) Expansion NPC Cohort (MEDI4736 10 mg/kg Q2W)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 4/4 (100%) 2/4 (50%) 0/3 (0%) 3/3 (100%) 6/6 (100%) 4/7 (57.1%) 17/21 (81%) 42/62 (67.7%) 17/22 (77.3%) 208/304 (68.4%) 30/40 (75%) 8/21 (38.1%) 19/24 (79.2%) 42/51 (82.4%) 23/40 (57.5%) 23/31 (74.2%) 128/201 (63.7%) 16/20 (80%) 36/47 (76.6%) 16/20 (80%) 17/21 (81%) 35/62 (56.5%) 7/10 (70%)
    Serious Adverse Events
    Escalation Cohort (MEDI4736 0.1 mg/kg Q2W) Escalation Cohort (MEDI4736 0.3 mg/kg Q2W) Escalation Cohort (MEDI4736 1 mg/kg Q2W) Escalation Cohort (MEDI4736 3 mg/kg Q2W) Escalation Cohort (MEDI4736 10 mg/kg Q2W) Escalation Cohort (MEDI4736 15 mg/kg Q3W) Exploration Durvalumab 20 mg/kg (Q4W) Expansion SCCHN Cohort (MEDI4736 10 mg/kg Q2W) Expansion Non-SCCHN HPV Positive Cohort (MEDI4736 10 mg/kg Q2W) Expansion NSCLC Cohort (MEDI4736 10 mg/kg Q2W) Expansion HCC Total Cohort (MEDI4736 10 mg/kg Q2W) Expansion ACM Cohort (MEDI4736 10 mg/kg Q2W) Expansion UM Cohort (MEDI4736 10 mg/kg Q2W) Expansion GEC Cohort (MEDI4736 10 mg/kg Q2W) Expansion TNBC Cohort (MEDI4736 10 mg/kg Q2W) Expansion PAC Cohort (MEDI4736 10 mg/kg Q2W) Expansion UC Cohort (MEDI4736 10 mg/kg Q2W) Expansion GBM Cohort (MEDI4736 10 mg/kg Q2W) Expansion OC Cohort (MEDI4736 10 mg/kg Q2W) Expansion STS Cohort (MEDI4736 10 mg/kg Q2W) Expansion SCLC Cohort (MEDI4736 10 mg/kg Q2W) Expansion MSI-high Cancer Cohort (MEDI4736 10 mg/kg Q2W) Expansion NPC Cohort (MEDI4736 10 mg/kg Q2W)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 1/4 (25%) 2/4 (50%) 1/3 (33.3%) 1/3 (33.3%) 3/6 (50%) 3/7 (42.9%) 13/21 (61.9%) 30/62 (48.4%) 16/22 (72.7%) 163/304 (53.6%) 24/40 (60%) 7/21 (33.3%) 12/24 (50%) 26/51 (51%) 20/40 (50%) 25/31 (80.6%) 117/201 (58.2%) 9/20 (45%) 26/47 (55.3%) 7/20 (35%) 14/21 (66.7%) 31/62 (50%) 7/10 (70%)
    Blood and lymphatic system disorders
    Anaemia 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 1/22 (4.5%) 1 1/304 (0.3%) 1 0/40 (0%) 0 0/21 (0%) 0 1/24 (4.2%) 1 1/51 (2%) 1 0/40 (0%) 0 1/31 (3.2%) 1 3/201 (1.5%) 4 0/20 (0%) 0 0/47 (0%) 0 1/20 (5%) 1 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Disseminated intravascular coagulation 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 1/304 (0.3%) 2 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 1/201 (0.5%) 1 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Immune thrombocytopenic purpura 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 1/40 (2.5%) 3 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Leukocytosis 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 1/62 (1.6%) 1 0/22 (0%) 0 1/304 (0.3%) 1 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 1/40 (2.5%) 1 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Lymph node pain 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 1/304 (0.3%) 1 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Neutropenia 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 1/304 (0.3%) 2 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Thrombocytopenia 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 1/21 (4.8%) 1 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 1/40 (2.5%) 2 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Thrombocytosis 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 1/62 (1.6%) 1 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Cardiac disorders
    Acute coronary syndrome 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 1/62 (1.6%) 1 0/10 (0%) 0
    Angina pectoris 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 1/24 (4.2%) 1 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Atrial fibrillation 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 1/21 (4.8%) 1 0/62 (0%) 0 0/22 (0%) 0 3/304 (1%) 3 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 1/201 (0.5%) 1 0/20 (0%) 0 1/47 (2.1%) 1 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Atrial flutter 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 3/304 (1%) 5 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 1/21 (4.8%) 1 0/62 (0%) 0 0/10 (0%) 0
    Atrioventricular block first degree 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 1/40 (2.5%) 1 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Cardiac arrest 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 2/304 (0.7%) 2 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Cardiac failure 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 1/304 (0.3%) 1 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Cardiac failure congestive 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 1/7 (14.3%) 2 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Cardiac tamponade 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 1/304 (0.3%) 1 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 1/47 (2.1%) 1 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Cardio-respiratory arrest 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 2/201 (1%) 2 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Cardiovascular disorder 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 1/31 (3.2%) 1 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Ischaemic cardiomyopathy 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 1/304 (0.3%) 1 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Myocardial infarction 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 1/21 (4.8%) 1 0/62 (0%) 0 0/22 (0%) 0 1/304 (0.3%) 1 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Myocarditis 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 1/31 (3.2%) 1 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Palpitations 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 1/304 (0.3%) 1 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Pericardial effusion 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 1/22 (4.5%) 1 3/304 (1%) 4 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 1/47 (2.1%) 1 0/20 (0%) 0 1/21 (4.8%) 1 0/62 (0%) 0 0/10 (0%) 0
    Sinus tachycardia 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 1/304 (0.3%) 1 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Supraventricular tachycardia 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 1/20 (5%) 1 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Trifascicular block 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 1/40 (2.5%) 1 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Ventricular tachycardia 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 1/304 (0.3%) 1 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Endocrine disorders
    Adrenal insufficiency 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 1/304 (0.3%) 1 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Hyperthyroidism 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 1/47 (2.1%) 1 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Steroid withdrawal syndrome 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 1/304 (0.3%) 1 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Gastrointestinal disorders
    Abdominal pain 0/4 (0%) 0 1/4 (25%) 1 0/3 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/7 (0%) 0 2/21 (9.5%) 2 0/62 (0%) 0 2/22 (9.1%) 3 3/304 (1%) 3 0/40 (0%) 0 0/21 (0%) 0 1/24 (4.2%) 1 2/51 (3.9%) 3 2/40 (5%) 2 3/31 (9.7%) 3 5/201 (2.5%) 5 0/20 (0%) 0 3/47 (6.4%) 3 0/20 (0%) 0 0/21 (0%) 0 3/62 (4.8%) 3 1/10 (10%) 1
    Abdominal pain lower 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 1/62 (1.6%) 1 0/10 (0%) 0
    Abdominal pain upper 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 3/22 (13.6%) 3 2/304 (0.7%) 2 1/40 (2.5%) 1 0/21 (0%) 0 1/24 (4.2%) 1 0/51 (0%) 0 1/40 (2.5%) 1 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 1/47 (2.1%) 1 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Ascites 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 1/304 (0.3%) 2 2/40 (5%) 2 0/21 (0%) 0 0/24 (0%) 0 3/51 (5.9%) 3 0/40 (0%) 0 1/31 (3.2%) 1 0/201 (0%) 0 0/20 (0%) 0 1/47 (2.1%) 1 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Colitis 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 4/304 (1.3%) 5 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 2/47 (4.3%) 2 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Colitis ischaemic 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 1/304 (0.3%) 2 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Colonic fistula 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 1/201 (0.5%) 1 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Constipation 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 1/62 (1.6%) 1 0/22 (0%) 0 1/304 (0.3%) 1 0/40 (0%) 0 1/21 (4.8%) 1 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 1/31 (3.2%) 1 2/201 (1%) 2 0/20 (0%) 0 1/47 (2.1%) 1 0/20 (0%) 0 1/21 (4.8%) 1 0/62 (0%) 0 0/10 (0%) 0
    Diarrhoea 0/4 (0%) 0 1/4 (25%) 1 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 1/304 (0.3%) 1 0/40 (0%) 0 1/21 (4.8%) 1 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 1/47 (2.1%) 1 0/20 (0%) 0 0/21 (0%) 0 1/62 (1.6%) 1 0/10 (0%) 0
    Duodenal obstruction 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 1/304 (0.3%) 1 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Duodenal stenosis 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 1/31 (3.2%) 1 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Dysphagia 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 4/304 (1.3%) 4 0/40 (0%) 0 1/21 (4.8%) 1 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 1/47 (2.1%) 1 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Enterovesical fistula 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 1/201 (0.5%) 1 0/20 (0%) 0 0/47 (0%) 0 1/20 (5%) 1 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Faecaloma 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 1/201 (0.5%) 1 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Gastric perforation 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 1/47 (2.1%) 1 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Gastrointestinal haemorrhage 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 1/40 (2.5%) 1 0/21 (0%) 0 0/24 (0%) 0 1/51 (2%) 2 0/40 (0%) 0 0/31 (0%) 0 2/201 (1%) 2 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Haematemesis 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 1/51 (2%) 1 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Ileus 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 1/201 (0.5%) 1 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 1/62 (1.6%) 2 0/10 (0%) 0
    Intestinal ischaemia 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 1/304 (0.3%) 1 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Intestinal obstruction 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 1/304 (0.3%) 1 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 1/47 (2.1%) 1 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Intestinal perforation 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 1/22 (4.5%) 1 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Intra-abdominal haemorrhage 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 1/21 (4.8%) 1 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Large intestinal obstruction 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 1/47 (2.1%) 1 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Lower gastrointestinal haemorrhage 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 1/201 (0.5%) 1 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Nausea 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 1/22 (4.5%) 1 1/304 (0.3%) 2 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 1/51 (2%) 1 0/40 (0%) 0 1/31 (3.2%) 1 3/201 (1.5%) 4 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Pancreatitis 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 1/304 (0.3%) 1 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Proctalgia 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 1/62 (1.6%) 1 0/10 (0%) 0
    Proctitis 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 1/47 (2.1%) 1 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Retroperitoneal haemorrhage 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Small intestinal obstruction 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 1/22 (4.5%) 1 1/304 (0.3%) 1 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 1/51 (2%) 2 0/40 (0%) 0 0/31 (0%) 0 2/201 (1%) 2 0/20 (0%) 0 1/47 (2.1%) 1 0/20 (0%) 0 0/21 (0%) 0 1/62 (1.6%) 1 0/10 (0%) 0
    Small intestinal perforation 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 1/31 (3.2%) 1 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Subileus 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 1/201 (0.5%) 3 0/20 (0%) 0 1/47 (2.1%) 1 0/20 (0%) 0 0/21 (0%) 0 1/62 (1.6%) 1 0/10 (0%) 0
    Upper gastrointestinal haemorrhage 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 1/40 (2.5%) 1 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 1/47 (2.1%) 1 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Varices oesophageal 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 1/40 (2.5%) 1 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Vomiting 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 1/22 (4.5%) 1 2/304 (0.7%) 2 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 1/51 (2%) 1 0/40 (0%) 0 2/31 (6.5%) 2 5/201 (2.5%) 6 0/20 (0%) 0 1/47 (2.1%) 1 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    General disorders
    Asthenia 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 1/304 (0.3%) 1 2/40 (5%) 2 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 2/201 (1%) 2 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 1/21 (4.8%) 1 0/62 (0%) 0 0/10 (0%) 0
    Chest pain 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 1/304 (0.3%) 1 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Chills 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 1/201 (0.5%) 1 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Complication associated with device 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 1/10 (10%) 1
    Death 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 1/62 (1.6%) 1 0/22 (0%) 0 1/304 (0.3%) 1 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 2/40 (5%) 2 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Fatigue 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 4/304 (1.3%) 4 1/40 (2.5%) 1 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 2/201 (1%) 2 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 2/21 (9.5%) 2 0/62 (0%) 0 0/10 (0%) 0
    General physical health deterioration 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 3/304 (1%) 6 3/40 (7.5%) 5 0/21 (0%) 0 1/24 (4.2%) 1 1/51 (2%) 2 1/40 (2.5%) 2 0/31 (0%) 0 7/201 (3.5%) 11 0/20 (0%) 0 1/47 (2.1%) 2 0/20 (0%) 0 0/21 (0%) 0 3/62 (4.8%) 5 0/10 (0%) 0
    Malaise 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 1/40 (2.5%) 1 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Multiple organ dysfunction syndrome 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 1/10 (10%) 1
    Non-cardiac chest pain 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 3/304 (1%) 3 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 1/47 (2.1%) 1 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Oedema 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 1/304 (0.3%) 1 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Oedema peripheral 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 2/304 (0.7%) 2 1/40 (2.5%) 1 0/21 (0%) 0 1/24 (4.2%) 1 0/51 (0%) 0 0/40 (0%) 0 1/31 (3.2%) 1 1/201 (0.5%) 1 0/20 (0%) 0 0/47 (0%) 0 1/20 (5%) 1 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Pain 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 1/62 (1.6%) 1 0/22 (0%) 0 1/304 (0.3%) 1 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 1/40 (2.5%) 1 1/31 (3.2%) 1 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 1/20 (5%) 1 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Pyrexia 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 1/7 (14.3%) 1 1/21 (4.8%) 1 3/62 (4.8%) 3 0/22 (0%) 0 3/304 (1%) 4 2/40 (5%) 2 0/21 (0%) 0 2/24 (8.3%) 2 1/51 (2%) 1 2/40 (5%) 2 2/31 (6.5%) 3 3/201 (1.5%) 3 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 3/62 (4.8%) 4 0/10 (0%) 0
    Hepatobiliary disorders
    Autoimmune hepatitis 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 2/201 (1%) 3 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Cholangitis 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 1/31 (3.2%) 1 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Cholecystitis 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 1/22 (4.5%) 1 1/304 (0.3%) 1 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Cholelithiasis 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 1/22 (4.5%) 1 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 1/20 (5%) 1 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Chronic hepatic failure 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 1/201 (0.5%) 2 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Hepatic failure 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 1/40 (2.5%) 1 0/21 (0%) 0 2/24 (8.3%) 2 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 1/201 (0.5%) 1 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Hepatic function abnormal 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 1/51 (2%) 1 2/40 (5%) 2 0/31 (0%) 0 1/201 (0.5%) 1 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 1/62 (1.6%) 1 0/10 (0%) 0
    Hepatic haemorrhage 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 1/40 (2.5%) 1 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Hepatic vein thrombosis 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 1/304 (0.3%) 1 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Hepatobiliary disease 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 1/62 (1.6%) 1 0/10 (0%) 0
    Hepatocellular injury 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 1/62 (1.6%) 1 0/10 (0%) 0
    Hyperbilirubinaemia 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 1/304 (0.3%) 1 1/40 (2.5%) 2 0/21 (0%) 0 1/24 (4.2%) 1 1/51 (2%) 1 0/40 (0%) 0 1/31 (3.2%) 1 1/201 (0.5%) 1 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Liver injury 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 1/51 (2%) 1 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Infections and infestations
    Abdominal abscess 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 1/62 (1.6%) 1 0/10 (0%) 0
    Abdominal infection 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 1/22 (4.5%) 1 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Bacteraemia 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 1/21 (4.8%) 1 0/62 (0%) 0 1/22 (4.5%) 1 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 1/62 (1.6%) 1 0/10 (0%) 0
    Bartholinitis 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 1/304 (0.3%) 1 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Bronchitis 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 1/304 (0.3%) 1 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Cellulitis 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 1/62 (1.6%) 1 0/10 (0%) 0
    Clostridium difficile colitis 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 1/62 (1.6%) 1 0/10 (0%) 0
    Clostridium difficile infection 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 1/51 (2%) 1 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Device related infection 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 1/62 (1.6%) 1 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 1/51 (2%) 1 0/40 (0%) 0 0/31 (0%) 0 2/201 (1%) 2 0/20 (0%) 0 1/47 (2.1%) 1 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Diverticulitis 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 2/304 (0.7%) 2 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Erysipelas 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 1/201 (0.5%) 1 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Herpes zoster 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 1/304 (0.3%) 1 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Infected fistula 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 1/62 (1.6%) 1 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 1/62 (1.6%) 1 0/10 (0%) 0
    Kidney infection 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 1/62 (1.6%) 2 0/10 (0%) 0
    Necrotising fasciitis 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 1/304 (0.3%) 1 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Osteomyelitis 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 1/22 (4.5%) 1 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Peritonitis 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 1/304 (0.3%) 1 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 1/51 (2%) 1 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Peritonitis bacterial 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 1/40 (2.5%) 1 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Pneumonia 0/4 (0%) 0 1/4 (25%) 1 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 2/21 (9.5%) 2 2/62 (3.2%) 4 1/22 (4.5%) 1 21/304 (6.9%) 29 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 2/51 (3.9%) 2 1/40 (2.5%) 1 0/31 (0%) 0 4/201 (2%) 5 0/20 (0%) 0 0/47 (0%) 0 1/20 (5%) 1 2/21 (9.5%) 2 0/62 (0%) 0 0/10 (0%) 0
    Postoperative wound infection 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 1/201 (0.5%) 1 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Pulmonary tuberculosis 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 1/201 (0.5%) 1 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Pyelonephritis 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 1/201 (0.5%) 1 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 1/62 (1.6%) 3 0/10 (0%) 0
    Respiratory tract infection 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 2/304 (0.7%) 2 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Sepsis 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 1/21 (4.8%) 1 2/62 (3.2%) 3 1/22 (4.5%) 2 6/304 (2%) 8 1/40 (2.5%) 1 0/21 (0%) 0 0/24 (0%) 0 1/51 (2%) 1 0/40 (0%) 0 1/31 (3.2%) 1 8/201 (4%) 10 0/20 (0%) 0 2/47 (4.3%) 2 1/20 (5%) 1 0/21 (0%) 0 1/62 (1.6%) 1 0/10 (0%) 0
    Septic shock 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 1/40 (2.5%) 1 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Sinusitis 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 1/10 (10%) 1
    Stoma site infection 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 1/201 (0.5%) 1 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Subcutaneous abscess 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 1/201 (0.5%) 1 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Upper respiratory tract infection 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 2/304 (0.7%) 2 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Urinary tract candidiasis 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 1/201 (0.5%) 1 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Urinary tract infection 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 1/22 (4.5%) 1 1/304 (0.3%) 1 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 1/40 (2.5%) 1 1/31 (3.2%) 1 9/201 (4.5%) 13 0/20 (0%) 0 2/47 (4.3%) 2 0/20 (0%) 0 0/21 (0%) 0 2/62 (3.2%) 2 0/10 (0%) 0
    Urosepsis 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 1/304 (0.3%) 2 1/40 (2.5%) 1 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 1/201 (0.5%) 1 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Injury, poisoning and procedural complications
    Contusion 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 1/201 (0.5%) 1 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Fall 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 1/20 (5%) 1 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 1/62 (1.6%) 1 0/10 (0%) 0
    Femoral neck fracture 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 1/304 (0.3%) 1 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Femur fracture 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 1/201 (0.5%) 1 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Fracture 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 1/304 (0.3%) 1 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Hip fracture 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 1/304 (0.3%) 1 1/40 (2.5%) 1 0/21 (0%) 0 1/24 (4.2%) 1 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 1/201 (0.5%) 1 0/20 (0%) 0 1/47 (2.1%) 1 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Infusion related reaction 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 1/201 (0.5%) 1 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Post procedural complication 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 1/62 (1.6%) 1 0/10 (0%) 0
    Spinal compression fracture 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 1/201 (0.5%) 1 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Spinal fracture 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 1/62 (1.6%) 1 0/10 (0%) 0
    Toxicity to various agents 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 1/51 (2%) 1 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Investigations
    Alanine aminotransferase increased 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 1/201 (0.5%) 2 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Aspartate aminotransferase increased 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 1/40 (2.5%) 1 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 1/40 (2.5%) 1 0/31 (0%) 0 1/201 (0.5%) 2 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 1/21 (4.8%) 1 0/62 (0%) 0 0/10 (0%) 0
    Blood alkaline phosphatase increased 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 1/31 (3.2%) 1 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Blood bilirubin increased 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 1/304 (0.3%) 1 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 2/201 (1%) 2 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 1/21 (4.8%) 2 2/62 (3.2%) 2 0/10 (0%) 0
    Blood creatinine increased 0/4 (0%) 0 0/4 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 1/24 (4.2%) 1 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 1/201 (0.5%) 1 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Blood electrolytes decreased 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 1/304 (0.3%) 1 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Eastern cooperative oncology group performance status worsened 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 1/47 (2.1%) 1 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Gamma-glutamyltransferase increased 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 1/31 (3.2%) 1 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    International normalised ratio increased 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 1/201 (0.5%) 1 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Transaminases increased 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 1/24 (4.2%) 2 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Metabolism and nutrition disorders
    Decreased appetite 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 1/62 (1.6%) 1 0/22 (0%) 0 0/304 (0%) 0 1/40 (2.5%) 1 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Dehydration 0/4 (0%) 0 0/4 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 3/304 (1%) 3 1/40 (2.5%) 1 1/21 (4.8%) 1 0/24 (0%) 0 1/51 (2%) 1 2/40 (5%) 2 2/31 (6.5%) 2 3/201 (1.5%) 3 0/20 (0%) 0 1/47 (2.1%) 1 0/20 (0%) 0 0/21 (0%) 0 1/62 (1.6%) 1 0/10 (0%) 0
    Failure to thrive 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 1/304 (0.3%) 1 1/40 (2.5%) 1 0/21 (0%) 0 0/24 (0%) 0 1/51 (2%) 1 0/40 (0%) 0 0/31 (0%) 0 1/201 (0.5%) 1 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 1/62 (1.6%) 1 0/10 (0%) 0
    Hypercalcaemia 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 2/62 (3.2%) 2 0/22 (0%) 0 3/304 (1%) 3 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 5/201 (2.5%) 5 0/20 (0%) 0 1/47 (2.1%) 1 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Hyperglycaemia 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 1/10 (10%) 1
    Hyperkalaemia 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 1/51 (2%) 1 0/40 (0%) 0 0/31 (0%) 0 1/201 (0.5%) 1 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 1/62 (1.6%) 1 0/10 (0%) 0
    Hyperlipasaemia 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 1/201 (0.5%) 1 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Hypokalaemia 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 1/31 (3.2%) 1 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 1/21 (4.8%) 1 0/62 (0%) 0 0/10 (0%) 0
    Hypomagnesaemia 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 1/62 (1.6%) 1 0/10 (0%) 0
    Hyponatraemia 0/4 (0%) 0 0/4 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 1/62 (1.6%) 5 0/22 (0%) 0 1/304 (0.3%) 1 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 3/51 (5.9%) 3 0/40 (0%) 0 0/31 (0%) 0 2/201 (1%) 2 0/20 (0%) 0 0/47 (0%) 0 2/20 (10%) 2 0/21 (0%) 0 1/62 (1.6%) 1 0/10 (0%) 0
    Hypophagia 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 1/201 (0.5%) 1 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Lactic acidosis 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 1/201 (0.5%) 1 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Metabolic acidosis 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 1/201 (0.5%) 1 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Tumour lysis syndrome 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 1/62 (1.6%) 2 0/10 (0%) 0
    Musculoskeletal and connective tissue disorders
    Arthralgia 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 1/304 (0.3%) 1 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 1/201 (0.5%) 1 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Back pain 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 1/21 (4.8%) 1 0/62 (0%) 0 1/22 (4.5%) 1 4/304 (1.3%) 4 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 1/51 (2%) 1 1/40 (2.5%) 1 0/31 (0%) 0 9/201 (4.5%) 10 0/20 (0%) 0 1/47 (2.1%) 1 0/20 (0%) 0 1/21 (4.8%) 1 1/62 (1.6%) 1 0/10 (0%) 0
    Bone pain 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 2/304 (0.7%) 2 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Flank pain 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 1/304 (0.3%) 1 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 2/201 (1%) 2 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Groin pain 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 1/201 (0.5%) 1 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Muscular weakness 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 1/304 (0.3%) 1 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 1/31 (3.2%) 1 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Musculoskeletal chest pain 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 1/22 (4.5%) 1 1/304 (0.3%) 1 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 1/40 (2.5%) 1 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Musculoskeletal pain 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 1/40 (2.5%) 1 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 1/201 (0.5%) 1 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 1/62 (1.6%) 2 0/10 (0%) 0
    Myositis 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 1/201 (0.5%) 1 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Neck pain 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 1/62 (1.6%) 2 0/10 (0%) 0
    Pain in extremity 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 1/40 (2.5%) 1 1/21 (4.8%) 1 0/24 (0%) 0 0/51 (0%) 0 1/40 (2.5%) 1 0/31 (0%) 0 3/201 (1.5%) 3 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Pathological fracture 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 1/304 (0.3%) 1 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Polymyalgia rheumatica 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 1/201 (0.5%) 1 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Adenocarcinoma of the cervix 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 1/22 (4.5%) 1 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Adenocarcinoma pancreas 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 2/21 (9.5%) 2 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 3/31 (9.7%) 3 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Anal cancer 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 3/22 (13.6%) 3 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Bladder cancer 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 45/201 (22.4%) 50 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Bladder cancer stage iv 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 1/201 (0.5%) 2 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Bladder transitional cell carcinoma 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 4/201 (2%) 4 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Breast cancer metastatic 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 1/40 (2.5%) 1 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Cancer pain 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 3/201 (1.5%) 3 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Cervix carcinoma 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 2/22 (9.1%) 2 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Choroid melanoma 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 1/24 (4.2%) 1 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Colon cancer 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 2/62 (3.2%) 3 0/10 (0%) 0
    Colorectal adenocarcinoma 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 1/62 (1.6%) 1 0/10 (0%) 0
    Colorectal cancer 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 5/62 (8.1%) 6 0/10 (0%) 0
    Endometrial cancer 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 1/62 (1.6%) 1 0/10 (0%) 0
    Gastric cancer 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 4/51 (7.8%) 4 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Gastrooesophageal cancer 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 1/21 (4.8%) 1 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 1/51 (2%) 2 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Glioblastoma multiforme 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 2/20 (10%) 2 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Hepatocellular carcinoma 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 7/40 (17.5%) 8 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Intraocular melanoma 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 2/24 (8.3%) 2 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Lung adenocarcinoma 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 3/304 (1%) 3 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Lung cancer metastatic 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 3/304 (1%) 3 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Lung neoplasm 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 1/304 (0.3%) 1 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Lung neoplasm malignant 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 13/304 (4.3%) 14 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 1/21 (4.8%) 1 0/62 (0%) 0 0/10 (0%) 0
    Malignant melanoma 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 1/7 (14.3%) 1 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 2/21 (9.5%) 2 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Malignant neoplasm of renal pelvis 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 1/201 (0.5%) 1 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Malignant pleural effusion 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 1/51 (2%) 1 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Metastases to bladder 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 1/201 (0.5%) 1 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Metastatic carcinoma of the bladder 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 1/201 (0.5%) 1 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Metastatic gastric cancer 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 1/51 (2%) 1 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Metastatic malignant melanoma 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 2/21 (9.5%) 2 1/24 (4.2%) 1 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Nasopharyngeal cancer 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 4/10 (40%) 5
    Neoplasm swelling 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 1/304 (0.3%) 1 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Non-small cell lung cancer 1/4 (25%) 1 1/4 (25%) 1 0/3 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/7 (0%) 0 1/21 (4.8%) 1 0/62 (0%) 0 0/22 (0%) 0 47/304 (15.5%) 55 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Non-small cell lung cancer metastatic 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 1/304 (0.3%) 1 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Oesophageal adenocarcinoma 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 1/51 (2%) 1 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Oesophageal cancer metastatic 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 2/51 (3.9%) 2 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Oesophageal carcinoma 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 3/51 (5.9%) 4 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Oncologic complication 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 1/62 (1.6%) 1 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Ovarian cancer 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 7/47 (14.9%) 8 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Pancreatic carcinoma 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 1/21 (4.8%) 1 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 8/31 (25.8%) 9 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Pancreatic carcinoma metastatic 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 2/31 (6.5%) 2 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Pancreatic carcinoma stage iv 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 2/31 (6.5%) 2 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Paraneoplastic syndrome 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 1/51 (2%) 1 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 1/62 (1.6%) 1 0/10 (0%) 0
    Prostate cancer 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 1/62 (1.6%) 1 0/10 (0%) 0
    Small cell lung cancer 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 8/21 (38.1%) 13 0/62 (0%) 0 0/10 (0%) 0
    Soft tissue sarcoma 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 1/62 (1.6%) 1 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Squamous cell carcinoma 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 1/22 (4.5%) 1 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Squamous cell carcinoma of head and neck 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 6/62 (9.7%) 6 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Squamous cell carcinoma of lung 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 4/304 (1.3%) 6 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Squamous cell carcinoma of pharynx 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 2/62 (3.2%) 2 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Squamous cell carcinoma of the hypopharynx 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 2/62 (3.2%) 2 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Transitional cell cancer of the renal pelvis and ureter 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 1/201 (0.5%) 2 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Transitional cell carcinoma 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 8/201 (4%) 8 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Transitional cell carcinoma metastatic 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 1/201 (0.5%) 1 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Transitional cell carcinoma recurrent 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 1/201 (0.5%) 1 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Triple negative breast cancer 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 1/21 (4.8%) 1 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 2/40 (5%) 2 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Tumour associated fever 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 1/201 (0.5%) 1 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Tumour flare 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 1/201 (0.5%) 1 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Tumour pain 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 1/304 (0.3%) 1 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 1/51 (2%) 1 0/40 (0%) 0 0/31 (0%) 0 3/201 (1.5%) 3 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Vulval cancer metastatic 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 1/22 (4.5%) 1 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Nervous system disorders
    Aphasia 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 1/40 (2.5%) 1 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 1/21 (4.8%) 1 0/62 (0%) 0 0/10 (0%) 0
    Ataxia 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 1/40 (2.5%) 1 0/31 (0%) 0 0/201 (0%) 0 1/20 (5%) 1 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Basal ganglia infarction 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 1/47 (2.1%) 1 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Cauda equina syndrome 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 1/304 (0.3%) 1 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Cerebrovascular accident 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 1/21 (4.8%) 1 1/62 (1.6%) 1 0/22 (0%) 0 0/304 (0%) 0 1/40 (2.5%) 1 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 1/201 (0.5%) 2 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Cognitive disorder 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 1/40 (2.5%) 1 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Dizziness 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 1/201 (0.5%) 1 1/20 (5%) 1 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Dysarthria 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 1/62 (1.6%) 1 0/10 (0%) 0
    Facial paralysis 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 2/304 (0.7%) 2 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Headache 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 1/304 (0.3%) 1 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Hemianopia 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 1/304 (0.3%) 1 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Hemianopia homonymous 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 1/62 (1.6%) 1 0/10 (0%) 0
    Hemiparesis 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 1/304 (0.3%) 1 1/40 (2.5%) 1 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Hydrocephalus 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 1/304 (0.3%) 1 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Ischaemic neuropathy 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 1/40 (2.5%) 1 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Ischaemic stroke 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 1/304 (0.3%) 1 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Migraine 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 1/304 (0.3%) 2 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Monoparesis 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 1/201 (0.5%) 1 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Nerve compression 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 1/47 (2.1%) 1 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Nervous system disorder 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 3/20 (15%) 3 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Paraesthesia 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 2/40 (5%) 2 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 1/21 (4.8%) 1 0/62 (0%) 0 0/10 (0%) 0
    Partial seizures 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 1/40 (2.5%) 1 0/31 (0%) 0 0/201 (0%) 0 1/20 (5%) 1 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Peripheral motor neuropathy 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Peripheral sensory neuropathy 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 1/21 (4.8%) 1 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Seizure 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 1/304 (0.3%) 1 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 1/20 (5%) 1 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Spinal cord compression 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 1/40 (2.5%) 1 0/31 (0%) 0 1/201 (0.5%) 1 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 1/62 (1.6%) 1 1/10 (10%) 1
    Spinal cord oedema 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 1/40 (2.5%) 1 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Syncope 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 1/22 (4.5%) 1 1/304 (0.3%) 1 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 1/201 (0.5%) 1 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 1/62 (1.6%) 1 0/10 (0%) 0
    Transient ischaemic attack 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 2/304 (0.7%) 3 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Trigeminal neuralgia 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 1/304 (0.3%) 1 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Product Issues
    Device dislocation 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 1/201 (0.5%) 1 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Device malfunction 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 1/201 (0.5%) 1 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Device occlusion 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 1/31 (3.2%) 1 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Psychiatric disorders
    Anxiety 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 1/62 (1.6%) 1 0/10 (0%) 0
    Confusional state 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 1/40 (2.5%) 1 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 2/201 (1%) 3 1/20 (5%) 1 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Mental status changes 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 1/304 (0.3%) 1 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 1/20 (5%) 1 0/47 (0%) 0 0/20 (0%) 0 1/21 (4.8%) 1 0/62 (0%) 0 0/10 (0%) 0
    Suicide attempt 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 1/201 (0.5%) 1 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Renal and urinary disorders
    Acute kidney injury 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 1/304 (0.3%) 1 0/40 (0%) 0 0/21 (0%) 0 1/24 (4.2%) 1 3/51 (5.9%) 3 0/40 (0%) 0 1/31 (3.2%) 1 8/201 (4%) 9 0/20 (0%) 0 0/47 (0%) 0 1/20 (5%) 1 0/21 (0%) 0 1/62 (1.6%) 1 0/10 (0%) 0
    Azotaemia 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 1/201 (0.5%) 1 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Haematuria 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 2/201 (1%) 3 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Hydronephrosis 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 3/201 (1.5%) 3 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Hydroureter 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 1/40 (2.5%) 1 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Proteinuria 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 1/304 (0.3%) 1 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Ureteric obstruction 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 1/20 (5%) 1 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Urinary bladder polyp 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 1/201 (0.5%) 1 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Urinary tract obstruction 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 3/201 (1.5%) 5 0/20 (0%) 0 1/47 (2.1%) 1 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Urinary tract pain 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 1/201 (0.5%) 1 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Reproductive system and breast disorders
    Female genital tract fistula 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 1/201 (0.5%) 1 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Vaginal discharge 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 1/62 (1.6%) 1 0/10 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory failure 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 1/62 (1.6%) 1 0/22 (0%) 0 3/304 (1%) 3 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 1/201 (0.5%) 1 0/20 (0%) 0 0/47 (0%) 0 1/20 (5%) 2 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Bronchial obstruction 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 1/304 (0.3%) 1 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 1/51 (2%) 2 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Chronic obstructive pulmonary disease 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 5/304 (1.6%) 7 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Cough 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 1/304 (0.3%) 1 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 1/21 (4.8%) 1 0/62 (0%) 0 0/10 (0%) 0
    Dyspnoea 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 1/7 (14.3%) 1 0/21 (0%) 0 4/62 (6.5%) 5 0/22 (0%) 0 23/304 (7.6%) 24 1/40 (2.5%) 2 0/21 (0%) 0 0/24 (0%) 0 2/51 (3.9%) 2 2/40 (5%) 3 0/31 (0%) 0 2/201 (1%) 3 0/20 (0%) 0 0/47 (0%) 0 3/20 (15%) 3 4/21 (19%) 6 3/62 (4.8%) 3 0/10 (0%) 0
    Dyspnoea exertional 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 1/40 (2.5%) 1 0/31 (0%) 0 1/201 (0.5%) 1 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Haemoptysis 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 2/62 (3.2%) 4 0/22 (0%) 0 2/304 (0.7%) 2 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 1/21 (4.8%) 1 0/62 (0%) 0 0/10 (0%) 0
    Hypoxia 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 1/304 (0.3%) 2 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Obstructive airways disorder 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 1/304 (0.3%) 1 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Oesophagobronchial fistula 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 1/304 (0.3%) 1 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Pharyngeal haemorrhage 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 1/62 (1.6%) 2 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Pleural effusion 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 1/7 (14.3%) 2 0/21 (0%) 0 0/62 (0%) 0 1/22 (4.5%) 1 9/304 (3%) 9 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 2/40 (5%) 2 1/31 (3.2%) 1 2/201 (1%) 2 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 2/21 (9.5%) 3 0/62 (0%) 0 0/10 (0%) 0
    Pleuritic pain 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 3/304 (1%) 3 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Pneumonia aspiration 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 4/304 (1.3%) 6 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 1/51 (2%) 1 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Pneumonitis 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 4/304 (1.3%) 4 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 1/201 (0.5%) 2 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Pneumothorax 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 1/22 (4.5%) 1 2/304 (0.7%) 3 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 1/51 (2%) 2 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Pulmonary embolism 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 3/304 (1%) 3 0/40 (0%) 0 0/21 (0%) 0 1/24 (4.2%) 1 0/51 (0%) 0 0/40 (0%) 0 1/31 (3.2%) 1 2/201 (1%) 2 0/20 (0%) 0 2/47 (4.3%) 2 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Pulmonary haemorrhage 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 2/304 (0.7%) 3 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Pulmonary venous thrombosis 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 1/201 (0.5%) 1 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Respiratory distress 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 1/304 (0.3%) 1 0/40 (0%) 0 0/21 (0%) 0 1/24 (4.2%) 2 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Respiratory failure 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 1/21 (4.8%) 1 0/62 (0%) 0 0/22 (0%) 0 8/304 (2.6%) 9 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 2/51 (3.9%) 2 1/40 (2.5%) 2 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 1/20 (5%) 1 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Tracheal stenosis 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 1/21 (4.8%) 1 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Skin and subcutaneous tissue disorders
    Erythema 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 1/304 (0.3%) 1 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Vascular disorders
    Embolism 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 1/22 (4.5%) 1 4/304 (1.3%) 4 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 1/51 (2%) 2 0/40 (0%) 0 1/31 (3.2%) 1 0/201 (0%) 0 1/20 (5%) 1 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Haematoma 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 1/201 (0.5%) 1 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Hypertension 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 1/304 (0.3%) 1 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Hypotension 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 1/62 (1.6%) 1 0/22 (0%) 0 3/304 (1%) 3 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 1/201 (0.5%) 1 0/20 (0%) 0 1/47 (2.1%) 1 0/20 (0%) 0 0/21 (0%) 0 1/62 (1.6%) 1 0/10 (0%) 0
    Superior vena cava syndrome 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 1/62 (1.6%) 1 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 1/21 (4.8%) 1 0/62 (0%) 0 0/10 (0%) 0
    Vascular occlusion 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 1/51 (2%) 1 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Vena cava thrombosis 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 1/31 (3.2%) 1 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Venous thrombosis 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 1/201 (0.5%) 1 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Other (Not Including Serious) Adverse Events
    Escalation Cohort (MEDI4736 0.1 mg/kg Q2W) Escalation Cohort (MEDI4736 0.3 mg/kg Q2W) Escalation Cohort (MEDI4736 1 mg/kg Q2W) Escalation Cohort (MEDI4736 3 mg/kg Q2W) Escalation Cohort (MEDI4736 10 mg/kg Q2W) Escalation Cohort (MEDI4736 15 mg/kg Q3W) Exploration Durvalumab 20 mg/kg (Q4W) Expansion SCCHN Cohort (MEDI4736 10 mg/kg Q2W) Expansion Non-SCCHN HPV Positive Cohort (MEDI4736 10 mg/kg Q2W) Expansion NSCLC Cohort (MEDI4736 10 mg/kg Q2W) Expansion HCC Total Cohort (MEDI4736 10 mg/kg Q2W) Expansion ACM Cohort (MEDI4736 10 mg/kg Q2W) Expansion UM Cohort (MEDI4736 10 mg/kg Q2W) Expansion GEC Cohort (MEDI4736 10 mg/kg Q2W) Expansion TNBC Cohort (MEDI4736 10 mg/kg Q2W) Expansion PAC Cohort (MEDI4736 10 mg/kg Q2W) Expansion UC Cohort (MEDI4736 10 mg/kg Q2W) Expansion GBM Cohort (MEDI4736 10 mg/kg Q2W) Expansion OC Cohort (MEDI4736 10 mg/kg Q2W) Expansion STS Cohort (MEDI4736 10 mg/kg Q2W) Expansion SCLC Cohort (MEDI4736 10 mg/kg Q2W) Expansion MSI-high Cancer Cohort (MEDI4736 10 mg/kg Q2W) Expansion NPC Cohort (MEDI4736 10 mg/kg Q2W)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 3/4 (75%) 4/4 (100%) 3/3 (100%) 3/3 (100%) 6/6 (100%) 7/7 (100%) 20/21 (95.2%) 61/62 (98.4%) 22/22 (100%) 292/304 (96.1%) 40/40 (100%) 19/21 (90.5%) 22/24 (91.7%) 50/51 (98%) 39/40 (97.5%) 31/31 (100%) 194/201 (96.5%) 18/20 (90%) 46/47 (97.9%) 20/20 (100%) 17/21 (81%) 57/62 (91.9%) 10/10 (100%)
    Blood and lymphatic system disorders
    Anaemia 1/4 (25%) 1 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/7 (0%) 0 0/21 (0%) 0 10/62 (16.1%) 11 5/22 (22.7%) 7 47/304 (15.5%) 74 5/40 (12.5%) 6 3/21 (14.3%) 12 1/24 (4.2%) 1 7/51 (13.7%) 20 2/40 (5%) 7 4/31 (12.9%) 7 43/201 (21.4%) 72 2/20 (10%) 2 10/47 (21.3%) 12 8/20 (40%) 14 5/21 (23.8%) 5 11/62 (17.7%) 22 1/10 (10%) 1
    Leukopenia 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 3/304 (1%) 4 2/40 (5%) 3 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 1/201 (0.5%) 1 0/20 (0%) 0 1/47 (2.1%) 2 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Neutropenia 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 2/304 (0.7%) 8 1/40 (2.5%) 3 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 1/40 (2.5%) 1 0/31 (0%) 0 3/201 (1.5%) 5 1/20 (5%) 1 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Splenomegaly 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Thrombocytopenia 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 8/304 (2.6%) 12 2/40 (5%) 7 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 1/31 (3.2%) 1 5/201 (2.5%) 9 1/20 (5%) 1 3/47 (6.4%) 4 1/20 (5%) 2 1/21 (4.8%) 2 0/62 (0%) 0 1/10 (10%) 1
    Cardiac disorders
    Atrial fibrillation 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 1/7 (14.3%) 1 0/21 (0%) 0 1/62 (1.6%) 1 0/22 (0%) 0 5/304 (1.6%) 6 1/40 (2.5%) 3 0/21 (0%) 0 0/24 (0%) 0 1/51 (2%) 1 0/40 (0%) 0 0/31 (0%) 0 2/201 (1%) 5 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 1/21 (4.8%) 1 1/62 (1.6%) 1 0/10 (0%) 0
    Extrasystoles 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 1/7 (14.3%) 1 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 1/304 (0.3%) 1 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Palpitations 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 6/304 (2%) 7 2/40 (5%) 2 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 1/40 (2.5%) 1 0/31 (0%) 0 4/201 (2%) 4 0/20 (0%) 0 0/47 (0%) 0 1/20 (5%) 2 1/21 (4.8%) 1 0/62 (0%) 0 0/10 (0%) 0
    Ear and labyrinth disorders
    Ear pain 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 2/62 (3.2%) 2 1/22 (4.5%) 1 2/304 (0.7%) 3 1/40 (2.5%) 1 0/21 (0%) 0 0/24 (0%) 0 1/51 (2%) 1 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 1/20 (5%) 1 0/21 (0%) 0 0/62 (0%) 0 1/10 (10%) 1
    Eustachian tube dysfunction 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 1/10 (10%) 1
    Otorrhoea 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 1/62 (1.6%) 1 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 1/10 (10%) 1
    Endocrine disorders
    Hyperthyroidism 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 1/21 (4.8%) 1 0/62 (0%) 0 2/22 (9.1%) 2 12/304 (3.9%) 19 2/40 (5%) 2 0/21 (0%) 0 1/24 (4.2%) 1 1/51 (2%) 1 1/40 (2.5%) 1 0/31 (0%) 0 8/201 (4%) 10 0/20 (0%) 0 1/47 (2.1%) 1 0/20 (0%) 0 0/21 (0%) 0 1/62 (1.6%) 1 0/10 (0%) 0
    Hypothyroidism 0/4 (0%) 0 1/4 (25%) 1 1/3 (33.3%) 1 0/3 (0%) 0 0/6 (0%) 0 1/7 (14.3%) 1 3/21 (14.3%) 3 5/62 (8.1%) 5 3/22 (13.6%) 3 29/304 (9.5%) 34 4/40 (10%) 4 3/21 (14.3%) 4 1/24 (4.2%) 1 2/51 (3.9%) 2 4/40 (10%) 5 5/31 (16.1%) 6 17/201 (8.5%) 21 2/20 (10%) 2 4/47 (8.5%) 4 2/20 (10%) 3 0/21 (0%) 0 6/62 (9.7%) 6 1/10 (10%) 1
    Eye disorders
    Cataract 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 1/304 (0.3%) 1 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 2/201 (1%) 2 1/20 (5%) 1 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 1/10 (10%) 1
    Conjunctival hyperaemia 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 1/7 (14.3%) 1 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 1/304 (0.3%) 1 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Diplopia 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 2/62 (3.2%) 2 0/22 (0%) 0 2/304 (0.7%) 2 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 1/51 (2%) 1 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 1/10 (10%) 1
    Eye pain 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 1/22 (4.5%) 1 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 1/62 (1.6%) 1 0/10 (0%) 0
    Vision blurred 1/4 (25%) 1 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 1/21 (4.8%) 1 3/62 (4.8%) 3 2/22 (9.1%) 2 7/304 (2.3%) 7 2/40 (5%) 2 1/21 (4.8%) 1 1/24 (4.2%) 1 2/51 (3.9%) 4 2/40 (5%) 2 1/31 (3.2%) 1 2/201 (1%) 2 0/20 (0%) 0 2/47 (4.3%) 2 1/20 (5%) 1 1/21 (4.8%) 1 3/62 (4.8%) 4 0/10 (0%) 0
    Vitreous floaters 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 1/304 (0.3%) 1 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 1/40 (2.5%) 1 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Gastrointestinal disorders
    Abdominal discomfort 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 1/304 (0.3%) 1 1/40 (2.5%) 1 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 1/31 (3.2%) 1 2/201 (1%) 2 0/20 (0%) 0 3/47 (6.4%) 3 0/20 (0%) 0 1/21 (4.8%) 1 0/62 (0%) 0 0/10 (0%) 0
    Abdominal distension 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 2/21 (9.5%) 2 2/62 (3.2%) 2 1/22 (4.5%) 1 9/304 (3%) 10 5/40 (12.5%) 5 0/21 (0%) 0 1/24 (4.2%) 1 3/51 (5.9%) 3 0/40 (0%) 0 1/31 (3.2%) 1 6/201 (3%) 6 0/20 (0%) 0 2/47 (4.3%) 2 1/20 (5%) 2 1/21 (4.8%) 1 3/62 (4.8%) 3 0/10 (0%) 0
    Abdominal pain 0/4 (0%) 0 0/4 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/6 (0%) 0 2/7 (28.6%) 3 3/21 (14.3%) 3 5/62 (8.1%) 6 4/22 (18.2%) 5 23/304 (7.6%) 28 11/40 (27.5%) 12 1/21 (4.8%) 2 4/24 (16.7%) 4 13/51 (25.5%) 27 2/40 (5%) 4 9/31 (29%) 12 20/201 (10%) 25 1/20 (5%) 1 15/47 (31.9%) 23 3/20 (15%) 5 3/21 (14.3%) 3 12/62 (19.4%) 24 3/10 (30%) 3
    Abdominal pain lower 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 3/40 (7.5%) 3 0/21 (0%) 0 1/24 (4.2%) 1 1/51 (2%) 1 1/40 (2.5%) 1 1/31 (3.2%) 1 3/201 (1.5%) 3 0/20 (0%) 0 0/47 (0%) 0 2/20 (10%) 3 0/21 (0%) 0 3/62 (4.8%) 3 0/10 (0%) 0
    Abdominal pain upper 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 1/7 (14.3%) 1 1/21 (4.8%) 1 2/62 (3.2%) 2 3/22 (13.6%) 4 7/304 (2.3%) 7 8/40 (20%) 11 0/21 (0%) 0 4/24 (16.7%) 4 4/51 (7.8%) 4 4/40 (10%) 5 1/31 (3.2%) 1 5/201 (2.5%) 5 3/20 (15%) 3 1/47 (2.1%) 5 1/20 (5%) 2 1/21 (4.8%) 1 1/62 (1.6%) 1 1/10 (10%) 1
    Ascites 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 1/21 (4.8%) 1 0/62 (0%) 0 1/22 (4.5%) 1 2/304 (0.7%) 2 4/40 (10%) 6 0/21 (0%) 0 0/24 (0%) 0 5/51 (9.8%) 5 1/40 (2.5%) 1 2/31 (6.5%) 2 2/201 (1%) 2 0/20 (0%) 0 7/47 (14.9%) 11 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 1/10 (10%) 1
    Constipation 0/4 (0%) 0 1/4 (25%) 1 1/3 (33.3%) 2 0/3 (0%) 0 3/6 (50%) 3 1/7 (14.3%) 1 2/21 (9.5%) 2 10/62 (16.1%) 11 6/22 (27.3%) 7 48/304 (15.8%) 55 11/40 (27.5%) 12 4/21 (19%) 4 4/24 (16.7%) 4 16/51 (31.4%) 20 5/40 (12.5%) 5 9/31 (29%) 10 55/201 (27.4%) 63 2/20 (10%) 2 14/47 (29.8%) 16 3/20 (15%) 3 4/21 (19%) 4 13/62 (21%) 18 0/10 (0%) 0
    Diarrhoea 2/4 (50%) 2 2/4 (50%) 3 1/3 (33.3%) 4 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 1/21 (4.8%) 1 11/62 (17.7%) 18 6/22 (27.3%) 9 53/304 (17.4%) 96 10/40 (25%) 12 5/21 (23.8%) 8 5/24 (20.8%) 10 17/51 (33.3%) 19 5/40 (12.5%) 6 4/31 (12.9%) 5 36/201 (17.9%) 52 1/20 (5%) 2 11/47 (23.4%) 17 1/20 (5%) 1 0/21 (0%) 0 18/62 (29%) 37 0/10 (0%) 0
    Dry mouth 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 1/21 (4.8%) 1 4/62 (6.5%) 4 0/22 (0%) 0 17/304 (5.6%) 19 4/40 (10%) 4 1/21 (4.8%) 2 1/24 (4.2%) 1 5/51 (9.8%) 7 2/40 (5%) 2 4/31 (12.9%) 4 11/201 (5.5%) 14 0/20 (0%) 0 1/47 (2.1%) 1 0/20 (0%) 0 1/21 (4.8%) 1 5/62 (8.1%) 5 2/10 (20%) 2
    Dyspepsia 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 1/7 (14.3%) 1 1/21 (4.8%) 1 1/62 (1.6%) 1 0/22 (0%) 0 10/304 (3.3%) 11 4/40 (10%) 4 1/21 (4.8%) 1 2/24 (8.3%) 2 3/51 (5.9%) 3 1/40 (2.5%) 1 2/31 (6.5%) 2 12/201 (6%) 12 1/20 (5%) 1 5/47 (10.6%) 5 0/20 (0%) 0 1/21 (4.8%) 1 1/62 (1.6%) 1 0/10 (0%) 0
    Dysphagia 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 1/21 (4.8%) 1 5/62 (8.1%) 6 0/22 (0%) 0 15/304 (4.9%) 18 1/40 (2.5%) 1 0/21 (0%) 0 0/24 (0%) 0 10/51 (19.6%) 12 2/40 (5%) 6 0/31 (0%) 0 3/201 (1.5%) 3 1/20 (5%) 1 1/47 (2.1%) 1 1/20 (5%) 1 0/21 (0%) 0 3/62 (4.8%) 3 1/10 (10%) 1
    Eructation 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 1/304 (0.3%) 1 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 3/51 (5.9%) 9 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Flatulence 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 3/304 (1%) 3 1/40 (2.5%) 2 0/21 (0%) 0 0/24 (0%) 0 3/51 (5.9%) 9 1/40 (2.5%) 1 4/31 (12.9%) 4 1/201 (0.5%) 1 0/20 (0%) 0 2/47 (4.3%) 2 0/20 (0%) 0 1/21 (4.8%) 3 1/62 (1.6%) 1 0/10 (0%) 0
    Gastrooesophageal reflux disease 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 2/62 (3.2%) 2 0/22 (0%) 0 11/304 (3.6%) 13 2/40 (5%) 2 1/21 (4.8%) 1 1/24 (4.2%) 1 7/51 (13.7%) 18 2/40 (5%) 2 5/31 (16.1%) 5 4/201 (2%) 4 0/20 (0%) 0 3/47 (6.4%) 3 0/20 (0%) 0 3/21 (14.3%) 3 3/62 (4.8%) 3 0/10 (0%) 0
    Impaired gastric emptying 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 1/7 (14.3%) 1 0/21 (0%) 0 1/62 (1.6%) 1 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 1/31 (3.2%) 1 0/201 (0%) 0 0/20 (0%) 0 1/47 (2.1%) 1 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Loose tooth 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 1/10 (10%) 1
    Nausea 0/4 (0%) 0 1/4 (25%) 2 2/3 (66.7%) 6 0/3 (0%) 0 1/6 (16.7%) 1 3/7 (42.9%) 3 2/21 (9.5%) 2 12/62 (19.4%) 15 7/22 (31.8%) 8 67/304 (22%) 82 14/40 (35%) 16 5/21 (23.8%) 8 10/24 (41.7%) 14 13/51 (25.5%) 26 9/40 (22.5%) 9 10/31 (32.3%) 15 47/201 (23.4%) 70 5/20 (25%) 6 15/47 (31.9%) 25 2/20 (10%) 2 6/21 (28.6%) 6 18/62 (29%) 30 3/10 (30%) 3
    Oral pain 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 3/62 (4.8%) 3 0/22 (0%) 0 0/304 (0%) 0 1/40 (2.5%) 1 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 1/47 (2.1%) 1 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 1/10 (10%) 1
    Stomatitis 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 1/62 (1.6%) 1 0/22 (0%) 0 4/304 (1.3%) 5 1/40 (2.5%) 1 1/21 (4.8%) 1 0/24 (0%) 0 2/51 (3.9%) 5 0/40 (0%) 0 1/31 (3.2%) 1 7/201 (3.5%) 7 0/20 (0%) 0 1/47 (2.1%) 2 0/20 (0%) 0 0/21 (0%) 0 1/62 (1.6%) 1 1/10 (10%) 1
    Toothache 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 1/7 (14.3%) 1 1/21 (4.8%) 1 0/62 (0%) 0 0/22 (0%) 0 8/304 (2.6%) 12 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 1/40 (2.5%) 1 0/31 (0%) 0 2/201 (1%) 2 0/20 (0%) 0 1/47 (2.1%) 1 0/20 (0%) 0 0/21 (0%) 0 2/62 (3.2%) 2 0/10 (0%) 0
    Vomiting 1/4 (25%) 1 1/4 (25%) 2 0/3 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 2/7 (28.6%) 3 1/21 (4.8%) 1 10/62 (16.1%) 13 6/22 (27.3%) 10 41/304 (13.5%) 53 10/40 (25%) 16 5/21 (23.8%) 5 4/24 (16.7%) 4 10/51 (19.6%) 35 7/40 (17.5%) 8 8/31 (25.8%) 16 27/201 (13.4%) 39 3/20 (15%) 4 10/47 (21.3%) 15 2/20 (10%) 3 4/21 (19%) 5 8/62 (12.9%) 15 3/10 (30%) 3
    General disorders
    Asthenia 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 2 1/6 (16.7%) 1 2/7 (28.6%) 3 0/21 (0%) 0 2/62 (3.2%) 2 2/22 (9.1%) 4 14/304 (4.6%) 16 6/40 (15%) 12 1/21 (4.8%) 1 5/24 (20.8%) 6 3/51 (5.9%) 3 5/40 (12.5%) 6 0/31 (0%) 0 26/201 (12.9%) 44 2/20 (10%) 2 4/47 (8.5%) 6 1/20 (5%) 1 1/21 (4.8%) 2 10/62 (16.1%) 12 1/10 (10%) 1
    Chest discomfort 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 1/304 (0.3%) 2 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 3/201 (1.5%) 3 2/20 (10%) 2 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Chills 0/4 (0%) 0 1/4 (25%) 1 0/3 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/7 (0%) 0 2/21 (9.5%) 2 3/62 (4.8%) 4 2/22 (9.1%) 2 13/304 (4.3%) 13 3/40 (7.5%) 3 4/21 (19%) 4 1/24 (4.2%) 1 4/51 (7.8%) 4 0/40 (0%) 0 6/31 (19.4%) 7 8/201 (4%) 10 2/20 (10%) 2 4/47 (8.5%) 4 1/20 (5%) 1 0/21 (0%) 0 2/62 (3.2%) 3 0/10 (0%) 0
    Face oedema 0/4 (0%) 0 1/4 (25%) 1 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 2/62 (3.2%) 2 1/22 (4.5%) 1 1/304 (0.3%) 1 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 1/62 (1.6%) 1 0/10 (0%) 0
    Fatigue 1/4 (25%) 1 2/4 (50%) 3 1/3 (33.3%) 1 0/3 (0%) 0 3/6 (50%) 7 3/7 (42.9%) 5 8/21 (38.1%) 13 21/62 (33.9%) 29 11/22 (50%) 13 114/304 (37.5%) 165 20/40 (50%) 23 10/21 (47.6%) 10 9/24 (37.5%) 12 28/51 (54.9%) 73 7/40 (17.5%) 11 19/31 (61.3%) 24 73/201 (36.3%) 91 8/20 (40%) 8 19/47 (40.4%) 23 9/20 (45%) 11 6/21 (28.6%) 7 15/62 (24.2%) 19 4/10 (40%) 4
    Gait disturbance 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 1/7 (14.3%) 2 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 2/201 (1%) 2 2/20 (10%) 3 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 1/62 (1.6%) 1 0/10 (0%) 0
    General physical health deterioration 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 1/304 (0.3%) 1 2/40 (5%) 3 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 1/40 (2.5%) 1 0/31 (0%) 0 3/201 (1.5%) 4 0/20 (0%) 0 1/47 (2.1%) 1 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Hernia pain 0/4 (0%) 0 0/4 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Influenza like illness 0/4 (0%) 0 0/4 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 1/6 (16.7%) 1 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 7/304 (2.3%) 7 2/40 (5%) 2 1/21 (4.8%) 3 0/24 (0%) 0 1/51 (2%) 1 2/40 (5%) 2 1/31 (3.2%) 1 2/201 (1%) 2 0/20 (0%) 0 7/47 (14.9%) 8 1/20 (5%) 1 1/21 (4.8%) 1 0/62 (0%) 0 0/10 (0%) 0
    Mucosal inflammation 0/4 (0%) 0 1/4 (25%) 1 1/3 (33.3%) 2 0/3 (0%) 0 0/6 (0%) 0 1/7 (14.3%) 1 0/21 (0%) 0 0/62 (0%) 0 1/22 (4.5%) 1 4/304 (1.3%) 4 1/40 (2.5%) 1 1/21 (4.8%) 2 1/24 (4.2%) 1 2/51 (3.9%) 2 0/40 (0%) 0 0/31 (0%) 0 6/201 (3%) 6 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 1/62 (1.6%) 1 0/10 (0%) 0
    Non-cardiac chest pain 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 1/7 (14.3%) 1 1/21 (4.8%) 1 1/62 (1.6%) 1 0/22 (0%) 0 17/304 (5.6%) 18 1/40 (2.5%) 1 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 1/40 (2.5%) 1 1/31 (3.2%) 1 2/201 (1%) 2 0/20 (0%) 0 1/47 (2.1%) 4 0/20 (0%) 0 2/21 (9.5%) 4 0/62 (0%) 0 0/10 (0%) 0
    Oedema peripheral 0/4 (0%) 0 1/4 (25%) 1 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 1/7 (14.3%) 1 4/21 (19%) 5 5/62 (8.1%) 6 1/22 (4.5%) 4 31/304 (10.2%) 42 11/40 (27.5%) 17 3/21 (14.3%) 3 2/24 (8.3%) 3 5/51 (9.8%) 5 6/40 (15%) 8 3/31 (9.7%) 3 28/201 (13.9%) 33 1/20 (5%) 1 9/47 (19.1%) 12 3/20 (15%) 3 2/21 (9.5%) 2 7/62 (11.3%) 11 2/10 (20%) 2
    Pain 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 1/62 (1.6%) 1 1/22 (4.5%) 1 9/304 (3%) 11 1/40 (2.5%) 1 1/21 (4.8%) 1 0/24 (0%) 0 1/51 (2%) 1 0/40 (0%) 0 0/31 (0%) 0 4/201 (2%) 4 0/20 (0%) 0 3/47 (6.4%) 3 0/20 (0%) 0 0/21 (0%) 0 3/62 (4.8%) 3 0/10 (0%) 0
    Peripheral swelling 1/4 (25%) 1 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 1/22 (4.5%) 1 5/304 (1.6%) 5 2/40 (5%) 2 1/21 (4.8%) 1 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 1/201 (0.5%) 1 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 1/21 (4.8%) 1 1/62 (1.6%) 1 0/10 (0%) 0
    Pyrexia 0/4 (0%) 0 3/4 (75%) 3 0/3 (0%) 0 1/3 (33.3%) 1 0/6 (0%) 0 2/7 (28.6%) 2 1/21 (4.8%) 1 9/62 (14.5%) 17 4/22 (18.2%) 6 33/304 (10.9%) 45 6/40 (15%) 18 4/21 (19%) 5 2/24 (8.3%) 3 7/51 (13.7%) 14 6/40 (15%) 6 4/31 (12.9%) 4 28/201 (13.9%) 34 3/20 (15%) 3 8/47 (17%) 8 5/20 (25%) 8 0/21 (0%) 0 11/62 (17.7%) 22 0/10 (0%) 0
    Swelling face 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 1/62 (1.6%) 1 0/22 (0%) 0 1/304 (0.3%) 1 1/40 (2.5%) 1 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 1/201 (0.5%) 1 0/20 (0%) 0 1/47 (2.1%) 1 1/20 (5%) 1 0/21 (0%) 0 2/62 (3.2%) 2 0/10 (0%) 0
    Thirst 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 1/51 (2%) 1 1/40 (2.5%) 1 2/31 (6.5%) 2 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Hepatobiliary disorders
    Hepatic pain 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 2/40 (5%) 2 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 1/31 (3.2%) 1 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 2/62 (3.2%) 2 0/10 (0%) 0
    Hepatomegaly 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 2/40 (5%) 2 0/21 (0%) 0 1/24 (4.2%) 1 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 1/201 (0.5%) 1 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 1/21 (4.8%) 1 0/62 (0%) 0 0/10 (0%) 0
    Hyperbilirubinaemia 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 1/62 (1.6%) 1 0/22 (0%) 0 1/304 (0.3%) 1 3/40 (7.5%) 6 0/21 (0%) 0 0/24 (0%) 0 1/51 (2%) 1 1/40 (2.5%) 1 1/31 (3.2%) 5 1/201 (0.5%) 1 0/20 (0%) 0 1/47 (2.1%) 2 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Jaundice 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 2/304 (0.7%) 2 2/40 (5%) 2 0/21 (0%) 0 0/24 (0%) 0 1/51 (2%) 1 0/40 (0%) 0 0/31 (0%) 0 1/201 (0.5%) 1 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Ocular icterus 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 2/40 (5%) 3 0/21 (0%) 0 0/24 (0%) 0 1/51 (2%) 1 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Immune system disorders
    Food allergy 0/4 (0%) 0 0/4 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Infections and infestations
    Bronchitis 1/4 (25%) 1 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 2/21 (9.5%) 2 2/62 (3.2%) 2 2/22 (9.1%) 2 11/304 (3.6%) 12 2/40 (5%) 2 1/21 (4.8%) 1 0/24 (0%) 0 1/51 (2%) 1 2/40 (5%) 2 0/31 (0%) 0 3/201 (1.5%) 4 0/20 (0%) 0 0/47 (0%) 0 1/20 (5%) 1 0/21 (0%) 0 2/62 (3.2%) 2 0/10 (0%) 0
    Candida infection 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 1/62 (1.6%) 1 0/22 (0%) 0 2/304 (0.7%) 2 1/40 (2.5%) 1 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 4/201 (2%) 4 0/20 (0%) 0 1/47 (2.1%) 1 0/20 (0%) 0 0/21 (0%) 0 1/62 (1.6%) 1 1/10 (10%) 1
    Escherichia urinary tract infection 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 1/10 (10%) 1
    Eye infection 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 2/304 (0.7%) 2 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 1/10 (10%) 1
    Gingivitis 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 3/304 (1%) 3 2/40 (5%) 2 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Herpes zoster 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 1/62 (1.6%) 1 0/22 (0%) 0 6/304 (2%) 6 0/40 (0%) 0 1/21 (4.8%) 1 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 1/10 (10%) 1
    Influenza 1/4 (25%) 1 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 1/7 (14.3%) 1 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 5/304 (1.6%) 5 1/40 (2.5%) 1 0/21 (0%) 0 0/24 (0%) 0 1/51 (2%) 1 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Nasopharyngitis 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 3/62 (4.8%) 5 0/22 (0%) 0 8/304 (2.6%) 9 1/40 (2.5%) 1 0/21 (0%) 0 0/24 (0%) 0 1/51 (2%) 1 1/40 (2.5%) 1 0/31 (0%) 0 9/201 (4.5%) 12 0/20 (0%) 0 1/47 (2.1%) 1 0/20 (0%) 0 0/21 (0%) 0 4/62 (6.5%) 4 0/10 (0%) 0
    Onychomycosis 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 2/10 (20%) 2
    Oral candidiasis 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/7 (0%) 0 0/21 (0%) 0 1/62 (1.6%) 3 2/22 (9.1%) 2 13/304 (4.3%) 15 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 1/51 (2%) 1 1/40 (2.5%) 1 1/31 (3.2%) 1 4/201 (2%) 4 1/20 (5%) 1 0/47 (0%) 0 1/20 (5%) 1 0/21 (0%) 0 3/62 (4.8%) 3 1/10 (10%) 1
    Otitis externa 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 1/304 (0.3%) 1 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 1/10 (10%) 1
    Otitis media 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 1/10 (10%) 1
    Pneumonia 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 1/7 (14.3%) 1 0/21 (0%) 0 3/62 (4.8%) 3 1/22 (4.5%) 1 25/304 (8.2%) 34 2/40 (5%) 2 0/21 (0%) 0 0/24 (0%) 0 1/51 (2%) 1 1/40 (2.5%) 1 1/31 (3.2%) 1 5/201 (2.5%) 6 1/20 (5%) 1 0/47 (0%) 0 0/20 (0%) 0 2/21 (9.5%) 3 1/62 (1.6%) 1 0/10 (0%) 0
    Pyuria 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 1/7 (14.3%) 1 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 1/304 (0.3%) 1 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 2/201 (1%) 2 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Rhinitis 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 1/62 (1.6%) 1 2/22 (9.1%) 2 6/304 (2%) 6 1/40 (2.5%) 1 0/21 (0%) 0 1/24 (4.2%) 1 1/51 (2%) 1 0/40 (0%) 0 0/31 (0%) 0 2/201 (1%) 2 0/20 (0%) 0 0/47 (0%) 0 1/20 (5%) 2 0/21 (0%) 0 3/62 (4.8%) 3 0/10 (0%) 0
    Sinusitis 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 12/304 (3.9%) 14 2/40 (5%) 3 1/21 (4.8%) 1 0/24 (0%) 0 1/51 (2%) 1 0/40 (0%) 0 0/31 (0%) 0 4/201 (2%) 6 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 1/21 (4.8%) 1 2/62 (3.2%) 2 1/10 (10%) 1
    Skin infection 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 1/7 (14.3%) 1 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 1/304 (0.3%) 1 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 1/201 (0.5%) 1 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 2/62 (3.2%) 2 0/10 (0%) 0
    Upper respiratory tract infection 0/4 (0%) 0 1/4 (25%) 1 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 3/62 (4.8%) 8 0/22 (0%) 0 23/304 (7.6%) 29 1/40 (2.5%) 1 2/21 (9.5%) 2 4/24 (16.7%) 4 1/51 (2%) 2 0/40 (0%) 0 1/31 (3.2%) 1 3/201 (1.5%) 4 1/20 (5%) 1 4/47 (8.5%) 4 1/20 (5%) 1 0/21 (0%) 0 8/62 (12.9%) 8 0/10 (0%) 0
    Urinary tract infection 0/4 (0%) 0 0/4 (0%) 0 2/3 (66.7%) 5 0/3 (0%) 0 0/6 (0%) 0 1/7 (14.3%) 1 1/21 (4.8%) 1 2/62 (3.2%) 2 5/22 (22.7%) 8 15/304 (4.9%) 17 4/40 (10%) 6 0/21 (0%) 0 2/24 (8.3%) 2 3/51 (5.9%) 3 2/40 (5%) 2 3/31 (9.7%) 3 35/201 (17.4%) 55 0/20 (0%) 0 8/47 (17%) 8 4/20 (20%) 7 1/21 (4.8%) 2 10/62 (16.1%) 14 1/10 (10%) 2
    Vulvovaginal mycotic infection 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 2/304 (0.7%) 2 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 1/20 (5%) 1 1/21 (4.8%) 1 1/62 (1.6%) 2 1/10 (10%) 1
    Injury, poisoning and procedural complications
    Fall 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 2/62 (3.2%) 2 1/22 (4.5%) 1 7/304 (2.3%) 8 0/40 (0%) 0 0/21 (0%) 0 2/24 (8.3%) 3 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 6/201 (3%) 7 2/20 (10%) 3 3/47 (6.4%) 3 0/20 (0%) 0 0/21 (0%) 0 1/62 (1.6%) 1 0/10 (0%) 0
    Infusion related reaction 1/4 (25%) 3 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 1/21 (4.8%) 2 0/62 (0%) 0 0/22 (0%) 0 3/304 (1%) 4 0/40 (0%) 0 1/21 (4.8%) 1 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 1/31 (3.2%) 1 1/201 (0.5%) 1 0/20 (0%) 0 2/47 (4.3%) 2 2/20 (10%) 3 0/21 (0%) 0 2/62 (3.2%) 2 0/10 (0%) 0
    Scar 0/4 (0%) 0 1/4 (25%) 1 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Soft tissue injury 1/4 (25%) 1 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 1/24 (4.2%) 1 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Spinal column injury 1/4 (25%) 1 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 1/22 (4.5%) 3 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Investigations
    Activated partial thromboplastin time prolonged 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 1/62 (1.6%) 1 1/22 (4.5%) 2 3/304 (1%) 3 1/40 (2.5%) 1 0/21 (0%) 0 0/24 (0%) 0 1/51 (2%) 3 1/40 (2.5%) 1 2/31 (6.5%) 2 4/201 (2%) 6 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 1/21 (4.8%) 1 0/62 (0%) 0 0/10 (0%) 0
    Alanine aminotransferase increased 0/4 (0%) 0 0/4 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/6 (0%) 0 1/7 (14.3%) 1 2/21 (9.5%) 2 3/62 (4.8%) 3 2/22 (9.1%) 3 19/304 (6.3%) 25 9/40 (22.5%) 20 1/21 (4.8%) 2 1/24 (4.2%) 1 1/51 (2%) 1 4/40 (10%) 4 6/31 (19.4%) 14 17/201 (8.5%) 21 1/20 (5%) 1 7/47 (14.9%) 8 1/20 (5%) 2 0/21 (0%) 0 5/62 (8.1%) 9 0/10 (0%) 0
    Aspartate aminotransferase increased 0/4 (0%) 0 0/4 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/6 (0%) 0 1/7 (14.3%) 1 2/21 (9.5%) 2 4/62 (6.5%) 4 3/22 (13.6%) 3 20/304 (6.6%) 26 20/40 (50%) 30 2/21 (9.5%) 3 2/24 (8.3%) 2 3/51 (5.9%) 5 7/40 (17.5%) 12 5/31 (16.1%) 13 17/201 (8.5%) 21 0/20 (0%) 0 5/47 (10.6%) 6 1/20 (5%) 1 1/21 (4.8%) 1 5/62 (8.1%) 11 2/10 (20%) 4
    Blood alkaline phosphatase increased 0/4 (0%) 0 0/4 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 1/6 (16.7%) 1 0/7 (0%) 0 1/21 (4.8%) 1 4/62 (6.5%) 4 1/22 (4.5%) 1 16/304 (5.3%) 21 9/40 (22.5%) 14 0/21 (0%) 0 4/24 (16.7%) 4 3/51 (5.9%) 3 4/40 (10%) 4 5/31 (16.1%) 12 11/201 (5.5%) 12 0/20 (0%) 0 4/47 (8.5%) 6 3/20 (15%) 4 0/21 (0%) 0 4/62 (6.5%) 8 1/10 (10%) 1
    Blood bilirubin increased 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 1/21 (4.8%) 1 2/62 (3.2%) 2 2/22 (9.1%) 3 8/304 (2.6%) 12 6/40 (15%) 8 1/21 (4.8%) 1 3/24 (12.5%) 6 1/51 (2%) 3 1/40 (2.5%) 3 2/31 (6.5%) 3 5/201 (2.5%) 8 0/20 (0%) 0 2/47 (4.3%) 2 1/20 (5%) 1 0/21 (0%) 0 2/62 (3.2%) 3 1/10 (10%) 1
    Blood cholesterol increased 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 3/304 (1%) 3 0/40 (0%) 0 2/21 (9.5%) 5 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 1/62 (1.6%) 1 0/10 (0%) 0
    Blood creatinine increased 0/4 (0%) 0 1/4 (25%) 1 0/3 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 1/22 (4.5%) 2 12/304 (3.9%) 21 2/40 (5%) 2 1/21 (4.8%) 1 0/24 (0%) 0 2/51 (3.9%) 4 0/40 (0%) 0 0/31 (0%) 0 21/201 (10.4%) 27 0/20 (0%) 0 1/47 (2.1%) 1 2/20 (10%) 2 0/21 (0%) 0 1/62 (1.6%) 2 0/10 (0%) 0
    Blood electrolytes decreased 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 1/10 (10%) 1
    Blood fibrinogen increased 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 4/304 (1.3%) 4 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 3/31 (9.7%) 3 1/201 (0.5%) 1 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Blood magnesium decreased 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 2/201 (1%) 2 0/20 (0%) 0 1/47 (2.1%) 1 1/20 (5%) 1 0/21 (0%) 0 0/62 (0%) 0 1/10 (10%) 1
    Blood thyroid stimulating hormone increased 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 8/304 (2.6%) 10 2/40 (5%) 2 1/21 (4.8%) 1 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 1/31 (3.2%) 1 2/201 (1%) 2 0/20 (0%) 0 0/47 (0%) 0 2/20 (10%) 2 0/21 (0%) 0 0/62 (0%) 0 1/10 (10%) 1
    Cortisol decreased 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 1/7 (14.3%) 1 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Gamma-glutamyltransferase increased 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/7 (0%) 0 2/21 (9.5%) 2 5/62 (8.1%) 8 1/22 (4.5%) 1 12/304 (3.9%) 13 8/40 (20%) 10 0/21 (0%) 0 3/24 (12.5%) 5 3/51 (5.9%) 3 7/40 (17.5%) 11 7/31 (22.6%) 15 11/201 (5.5%) 14 0/20 (0%) 0 4/47 (8.5%) 7 2/20 (10%) 3 3/21 (14.3%) 3 4/62 (6.5%) 10 1/10 (10%) 1
    International normalised ratio increased 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 1/62 (1.6%) 2 0/22 (0%) 0 3/304 (1%) 4 2/40 (5%) 5 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 4/201 (2%) 6 0/20 (0%) 0 2/47 (4.3%) 2 1/20 (5%) 2 1/21 (4.8%) 2 1/62 (1.6%) 1 0/10 (0%) 0
    Transaminases increased 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 1/62 (1.6%) 1 0/22 (0%) 0 1/304 (0.3%) 2 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 1/40 (2.5%) 1 2/31 (6.5%) 3 2/201 (1%) 2 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Vitamin d decreased 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 1/10 (10%) 1
    Weight decreased 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/7 (0%) 0 2/21 (9.5%) 2 6/62 (9.7%) 6 2/22 (9.1%) 3 24/304 (7.9%) 30 2/40 (5%) 2 1/21 (4.8%) 2 0/24 (0%) 0 2/51 (3.9%) 2 0/40 (0%) 0 6/31 (19.4%) 8 16/201 (8%) 19 1/20 (5%) 1 9/47 (19.1%) 13 1/20 (5%) 3 2/21 (9.5%) 2 4/62 (6.5%) 7 2/10 (20%) 2
    Weight increased 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 3/62 (4.8%) 3 0/22 (0%) 0 9/304 (3%) 14 2/40 (5%) 2 1/21 (4.8%) 2 0/24 (0%) 0 1/51 (2%) 1 1/40 (2.5%) 1 0/31 (0%) 0 2/201 (1%) 3 1/20 (5%) 1 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 1/62 (1.6%) 1 1/10 (10%) 1
    White blood cell count increased 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/7 (0%) 0 1/21 (4.8%) 1 0/62 (0%) 0 1/22 (4.5%) 1 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 1/201 (0.5%) 1 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Metabolism and nutrition disorders
    Decreased appetite 0/4 (0%) 0 1/4 (25%) 1 1/3 (33.3%) 1 0/3 (0%) 0 2/6 (33.3%) 3 1/7 (14.3%) 1 7/21 (33.3%) 9 7/62 (11.3%) 7 4/22 (18.2%) 7 80/304 (26.3%) 112 15/40 (37.5%) 17 6/21 (28.6%) 6 5/24 (20.8%) 5 22/51 (43.1%) 38 6/40 (15%) 6 11/31 (35.5%) 12 51/201 (25.4%) 60 4/20 (20%) 5 14/47 (29.8%) 17 2/20 (10%) 3 4/21 (19%) 4 10/62 (16.1%) 14 1/10 (10%) 1
    Dehydration 0/4 (0%) 0 1/4 (25%) 1 0/3 (0%) 0 1/3 (33.3%) 1 1/6 (16.7%) 1 0/7 (0%) 0 3/21 (14.3%) 3 7/62 (11.3%) 8 2/22 (9.1%) 2 18/304 (5.9%) 24 0/40 (0%) 0 4/21 (19%) 4 1/24 (4.2%) 1 8/51 (15.7%) 11 2/40 (5%) 2 5/31 (16.1%) 6 9/201 (4.5%) 12 2/20 (10%) 2 5/47 (10.6%) 5 1/20 (5%) 1 1/21 (4.8%) 1 4/62 (6.5%) 4 2/10 (20%) 3
    Fluid intake reduced 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 1/7 (14.3%) 1 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 1/304 (0.3%) 1 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Hypercalcaemia 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/7 (0%) 0 0/21 (0%) 0 7/62 (11.3%) 7 0/22 (0%) 0 16/304 (5.3%) 19 3/40 (7.5%) 4 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 1/40 (2.5%) 1 0/31 (0%) 0 10/201 (5%) 15 0/20 (0%) 0 1/47 (2.1%) 1 0/20 (0%) 0 0/21 (0%) 0 2/62 (3.2%) 2 0/10 (0%) 0
    Hyperglycaemia 0/4 (0%) 0 0/4 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 2/62 (3.2%) 6 1/22 (4.5%) 3 12/304 (3.9%) 15 4/40 (10%) 4 0/21 (0%) 0 0/24 (0%) 0 2/51 (3.9%) 7 0/40 (0%) 0 2/31 (6.5%) 2 6/201 (3%) 6 0/20 (0%) 0 1/47 (2.1%) 1 0/20 (0%) 0 0/21 (0%) 0 1/62 (1.6%) 1 1/10 (10%) 2
    Hyperkalaemia 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 1/62 (1.6%) 2 0/22 (0%) 0 7/304 (2.3%) 7 1/40 (2.5%) 1 0/21 (0%) 0 2/24 (8.3%) 2 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 15/201 (7.5%) 20 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 2/62 (3.2%) 4 0/10 (0%) 0
    Hyperuricaemia 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 1/21 (4.8%) 1 0/62 (0%) 0 0/22 (0%) 0 6/304 (2%) 6 3/40 (7.5%) 4 1/21 (4.8%) 1 0/24 (0%) 0 1/51 (2%) 1 0/40 (0%) 0 0/31 (0%) 0 9/201 (4.5%) 9 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 2/62 (3.2%) 3 0/10 (0%) 0
    Hypoalbuminaemia 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 3/62 (4.8%) 4 1/22 (4.5%) 1 20/304 (6.6%) 22 4/40 (10%) 4 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 3/40 (7.5%) 4 2/31 (6.5%) 2 9/201 (4.5%) 10 0/20 (0%) 0 2/47 (4.3%) 2 0/20 (0%) 0 3/21 (14.3%) 3 3/62 (4.8%) 3 0/10 (0%) 0
    Hypocalcaemia 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 1/62 (1.6%) 1 0/22 (0%) 0 5/304 (1.6%) 6 1/40 (2.5%) 1 0/21 (0%) 0 0/24 (0%) 0 4/51 (7.8%) 6 1/40 (2.5%) 1 1/31 (3.2%) 1 1/201 (0.5%) 2 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 3/62 (4.8%) 9 0/10 (0%) 0
    Hypoglycaemia 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 2/304 (0.7%) 2 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 1/40 (2.5%) 1 1/31 (3.2%) 1 1/201 (0.5%) 1 0/20 (0%) 0 4/47 (8.5%) 5 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 1/10 (10%) 2
    Hypokalaemia 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 2/62 (3.2%) 2 1/22 (4.5%) 1 22/304 (7.2%) 29 2/40 (5%) 4 2/21 (9.5%) 3 0/24 (0%) 0 1/51 (2%) 1 2/40 (5%) 2 1/31 (3.2%) 1 11/201 (5.5%) 13 3/20 (15%) 3 4/47 (8.5%) 6 1/20 (5%) 1 1/21 (4.8%) 1 6/62 (9.7%) 6 0/10 (0%) 0
    Hypomagnesaemia 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 1/21 (4.8%) 1 3/62 (4.8%) 4 1/22 (4.5%) 1 13/304 (4.3%) 17 3/40 (7.5%) 6 2/21 (9.5%) 4 1/24 (4.2%) 1 2/51 (3.9%) 2 1/40 (2.5%) 1 2/31 (6.5%) 3 12/201 (6%) 15 0/20 (0%) 0 7/47 (14.9%) 8 0/20 (0%) 0 4/21 (19%) 5 4/62 (6.5%) 8 0/10 (0%) 0
    Hyponatraemia 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 1/7 (14.3%) 1 1/21 (4.8%) 1 5/62 (8.1%) 6 1/22 (4.5%) 1 31/304 (10.2%) 49 5/40 (12.5%) 8 0/21 (0%) 0 1/24 (4.2%) 3 5/51 (9.8%) 5 3/40 (7.5%) 5 3/31 (9.7%) 3 20/201 (10%) 25 0/20 (0%) 0 0/47 (0%) 0 1/20 (5%) 1 6/21 (28.6%) 7 4/62 (6.5%) 4 0/10 (0%) 0
    Iron deficiency 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 1/7 (14.3%) 1 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 1/304 (0.3%) 1 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 1/201 (0.5%) 1 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Polydipsia 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 1/20 (5%) 1 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 1/10 (10%) 1
    Musculoskeletal and connective tissue disorders
    Arthralgia 1/4 (25%) 1 2/4 (50%) 3 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 2/21 (9.5%) 3 4/62 (6.5%) 9 3/22 (13.6%) 3 44/304 (14.5%) 62 6/40 (15%) 6 9/21 (42.9%) 14 4/24 (16.7%) 5 1/51 (2%) 2 4/40 (10%) 5 3/31 (9.7%) 3 25/201 (12.4%) 40 1/20 (5%) 2 11/47 (23.4%) 15 5/20 (25%) 6 3/21 (14.3%) 3 9/62 (14.5%) 14 2/10 (20%) 2
    Back pain 0/4 (0%) 0 0/4 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 1/6 (16.7%) 1 0/7 (0%) 0 1/21 (4.8%) 1 7/62 (11.3%) 7 4/22 (18.2%) 4 49/304 (16.1%) 56 6/40 (15%) 6 3/21 (14.3%) 3 2/24 (8.3%) 5 13/51 (25.5%) 16 6/40 (15%) 6 8/31 (25.8%) 8 30/201 (14.9%) 44 2/20 (10%) 2 8/47 (17%) 8 4/20 (20%) 5 4/21 (19%) 4 14/62 (22.6%) 20 1/10 (10%) 2
    Coccydynia 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 2/21 (9.5%) 2 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Groin pain 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 3/62 (4.8%) 3 3/22 (13.6%) 6 1/304 (0.3%) 1 1/40 (2.5%) 1 0/21 (0%) 0 0/24 (0%) 0 1/51 (2%) 1 0/40 (0%) 0 0/31 (0%) 0 4/201 (2%) 4 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 1/62 (1.6%) 1 1/10 (10%) 1
    Joint swelling 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 1/304 (0.3%) 1 1/40 (2.5%) 1 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 3/47 (6.4%) 4 0/20 (0%) 0 0/21 (0%) 0 1/62 (1.6%) 1 0/10 (0%) 0
    Muscle spasms 0/4 (0%) 0 0/4 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 2/62 (3.2%) 2 1/22 (4.5%) 1 10/304 (3.3%) 10 1/40 (2.5%) 1 1/21 (4.8%) 1 4/24 (16.7%) 4 1/51 (2%) 1 1/40 (2.5%) 1 3/31 (9.7%) 3 7/201 (3.5%) 10 0/20 (0%) 0 2/47 (4.3%) 2 1/20 (5%) 1 1/21 (4.8%) 1 0/62 (0%) 0 0/10 (0%) 0
    Muscular weakness 0/4 (0%) 0 1/4 (25%) 1 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 2/21 (9.5%) 3 1/62 (1.6%) 1 0/22 (0%) 0 8/304 (2.6%) 11 1/40 (2.5%) 1 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 1/40 (2.5%) 1 1/31 (3.2%) 1 2/201 (1%) 3 2/20 (10%) 2 0/47 (0%) 0 0/20 (0%) 0 1/21 (4.8%) 1 1/62 (1.6%) 1 0/10 (0%) 0
    Musculoskeletal chest pain 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 1/7 (14.3%) 1 1/21 (4.8%) 1 5/62 (8.1%) 5 1/22 (4.5%) 1 25/304 (8.2%) 31 4/40 (10%) 4 3/21 (14.3%) 3 1/24 (4.2%) 1 1/51 (2%) 1 6/40 (15%) 9 1/31 (3.2%) 1 5/201 (2.5%) 8 0/20 (0%) 0 1/47 (2.1%) 1 4/20 (20%) 4 0/21 (0%) 0 1/62 (1.6%) 1 0/10 (0%) 0
    Musculoskeletal pain 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 2/7 (28.6%) 3 3/21 (14.3%) 3 2/62 (3.2%) 2 1/22 (4.5%) 2 18/304 (5.9%) 23 6/40 (15%) 8 2/21 (9.5%) 2 2/24 (8.3%) 2 5/51 (9.8%) 33 2/40 (5%) 3 2/31 (6.5%) 2 16/201 (8%) 23 1/20 (5%) 1 3/47 (6.4%) 4 3/20 (15%) 3 1/21 (4.8%) 1 3/62 (4.8%) 4 1/10 (10%) 1
    Myalgia 0/4 (0%) 0 1/4 (25%) 1 1/3 (33.3%) 1 0/3 (0%) 0 0/6 (0%) 0 1/7 (14.3%) 1 2/21 (9.5%) 3 7/62 (11.3%) 8 1/22 (4.5%) 1 31/304 (10.2%) 41 3/40 (7.5%) 5 2/21 (9.5%) 2 5/24 (20.8%) 7 3/51 (5.9%) 3 4/40 (10%) 5 3/31 (9.7%) 4 14/201 (7%) 23 1/20 (5%) 1 4/47 (8.5%) 5 0/20 (0%) 0 0/21 (0%) 0 5/62 (8.1%) 6 0/10 (0%) 0
    Neck pain 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 1/21 (4.8%) 1 7/62 (11.3%) 8 0/22 (0%) 0 7/304 (2.3%) 7 1/40 (2.5%) 1 2/21 (9.5%) 2 0/24 (0%) 0 2/51 (3.9%) 3 0/40 (0%) 0 0/31 (0%) 0 3/201 (1.5%) 3 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 1/62 (1.6%) 1 1/10 (10%) 1
    Pain in extremity 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 1/7 (14.3%) 1 2/21 (9.5%) 2 1/62 (1.6%) 1 1/22 (4.5%) 1 26/304 (8.6%) 32 3/40 (7.5%) 4 3/21 (14.3%) 3 0/24 (0%) 0 2/51 (3.9%) 2 2/40 (5%) 2 0/31 (0%) 0 11/201 (5.5%) 15 1/20 (5%) 1 1/47 (2.1%) 1 4/20 (20%) 4 0/21 (0%) 0 3/62 (4.8%) 3 0/10 (0%) 0
    Pain in jaw 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 3/62 (4.8%) 4 0/22 (0%) 0 1/304 (0.3%) 1 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 1/40 (2.5%) 1 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 1/10 (10%) 1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Cancer pain 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 3/304 (1%) 3 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 3/40 (7.5%) 3 0/31 (0%) 0 4/201 (2%) 6 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Tumour pain 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 1/62 (1.6%) 2 0/22 (0%) 0 4/304 (1.3%) 4 0/40 (0%) 0 2/21 (9.5%) 2 0/24 (0%) 0 1/51 (2%) 1 0/40 (0%) 0 0/31 (0%) 0 10/201 (5%) 12 0/20 (0%) 0 1/47 (2.1%) 1 0/20 (0%) 0 0/21 (0%) 0 2/62 (3.2%) 2 0/10 (0%) 0
    Nervous system disorders
    Aphasia 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 1/7 (14.3%) 1 1/21 (4.8%) 1 0/62 (0%) 0 0/22 (0%) 0 1/304 (0.3%) 1 1/40 (2.5%) 1 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 3/20 (15%) 3 0/47 (0%) 0 0/20 (0%) 0 1/21 (4.8%) 1 0/62 (0%) 0 0/10 (0%) 0
    Ataxia 0/4 (0%) 0 1/4 (25%) 1 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 2/304 (0.7%) 2 1/40 (2.5%) 1 1/21 (4.8%) 1 0/24 (0%) 0 1/51 (2%) 1 0/40 (0%) 0 0/31 (0%) 0 1/201 (0.5%) 1 1/20 (5%) 2 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Dizziness 0/4 (0%) 0 1/4 (25%) 2 2/3 (66.7%) 4 0/3 (0%) 0 0/6 (0%) 0 2/7 (28.6%) 2 1/21 (4.8%) 1 5/62 (8.1%) 7 0/22 (0%) 0 23/304 (7.6%) 24 6/40 (15%) 6 3/21 (14.3%) 4 2/24 (8.3%) 2 9/51 (17.6%) 22 4/40 (10%) 5 5/31 (16.1%) 5 11/201 (5.5%) 14 2/20 (10%) 3 5/47 (10.6%) 5 1/20 (5%) 1 3/21 (14.3%) 3 5/62 (8.1%) 9 0/10 (0%) 0
    Dizziness postural 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 2/21 (9.5%) 2 1/62 (1.6%) 1 0/22 (0%) 0 1/304 (0.3%) 1 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 1/47 (2.1%) 1 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Dysarthria 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 1/7 (14.3%) 2 1/21 (4.8%) 1 1/62 (1.6%) 1 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 1/51 (2%) 1 1/40 (2.5%) 2 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Dysgeusia 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 1/21 (4.8%) 1 0/62 (0%) 0 0/22 (0%) 0 5/304 (1.6%) 5 0/40 (0%) 0 0/21 (0%) 0 1/24 (4.2%) 1 0/51 (0%) 0 0/40 (0%) 0 2/31 (6.5%) 2 3/201 (1.5%) 3 1/20 (5%) 1 2/47 (4.3%) 2 0/20 (0%) 0 0/21 (0%) 0 1/62 (1.6%) 1 3/10 (30%) 3
    Headache 1/4 (25%) 1 1/4 (25%) 2 1/3 (33.3%) 2 0/3 (0%) 0 0/6 (0%) 0 1/7 (14.3%) 3 0/21 (0%) 0 8/62 (12.9%) 8 2/22 (9.1%) 3 33/304 (10.9%) 46 1/40 (2.5%) 1 2/21 (9.5%) 2 4/24 (16.7%) 5 5/51 (9.8%) 6 7/40 (17.5%) 8 7/31 (22.6%) 7 10/201 (5%) 15 9/20 (45%) 11 6/47 (12.8%) 7 2/20 (10%) 2 4/21 (19%) 4 9/62 (14.5%) 14 4/10 (40%) 5
    Hemiparesis 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 1/304 (0.3%) 2 1/40 (2.5%) 1 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 1/40 (2.5%) 1 0/31 (0%) 0 0/201 (0%) 0 2/20 (10%) 2 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Hypoaesthesia 1/4 (25%) 1 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 1/21 (4.8%) 1 0/62 (0%) 0 0/22 (0%) 0 3/304 (1%) 3 1/40 (2.5%) 1 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 1/31 (3.2%) 1 0/201 (0%) 0 1/20 (5%) 1 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 1/62 (1.6%) 1 2/10 (20%) 2
    Lethargy 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 3/304 (1%) 3 0/40 (0%) 0 2/21 (9.5%) 2 0/24 (0%) 0 2/51 (3.9%) 2 0/40 (0%) 0 0/31 (0%) 0 2/201 (1%) 2 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Nervous system disorder 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 2/20 (10%) 2 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Neuropathy peripheral 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 1/21 (4.8%) 1 3/62 (4.8%) 3 0/22 (0%) 0 7/304 (2.3%) 8 1/40 (2.5%) 1 1/21 (4.8%) 1 0/24 (0%) 0 4/51 (7.8%) 5 2/40 (5%) 2 2/31 (6.5%) 2 9/201 (4.5%) 10 0/20 (0%) 0 1/47 (2.1%) 1 2/20 (10%) 2 1/21 (4.8%) 2 0/62 (0%) 0 0/10 (0%) 0
    Paraesthesia 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 1/7 (14.3%) 1 1/21 (4.8%) 2 0/62 (0%) 0 1/22 (4.5%) 2 6/304 (2%) 7 0/40 (0%) 0 2/21 (9.5%) 2 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 1/31 (3.2%) 1 1/201 (0.5%) 2 0/20 (0%) 0 1/47 (2.1%) 1 0/20 (0%) 0 0/21 (0%) 0 4/62 (6.5%) 4 2/10 (20%) 2
    Parosmia 1/4 (25%) 1 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Peripheral motor neuropathy 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 1/7 (14.3%) 2 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Peripheral sensory neuropathy 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 2/304 (0.7%) 2 0/40 (0%) 0 2/21 (9.5%) 2 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 1/201 (0.5%) 1 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 3/62 (4.8%) 3 0/10 (0%) 0
    Somnolence 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/7 (0%) 0 0/21 (0%) 0 1/62 (1.6%) 1 0/22 (0%) 0 1/304 (0.3%) 1 3/40 (7.5%) 3 0/21 (0%) 0 1/24 (4.2%) 2 2/51 (3.9%) 2 0/40 (0%) 0 1/31 (3.2%) 1 1/201 (0.5%) 1 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 1/21 (4.8%) 1 0/62 (0%) 0 0/10 (0%) 0
    Syncope 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 4/62 (6.5%) 4 0/22 (0%) 0 1/304 (0.3%) 1 0/40 (0%) 0 0/21 (0%) 0 1/24 (4.2%) 1 0/51 (0%) 0 1/40 (2.5%) 1 0/31 (0%) 0 2/201 (1%) 2 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 1/21 (4.8%) 1 0/62 (0%) 0 0/10 (0%) 0
    Taste disorder 1/4 (25%) 1 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 4/304 (1.3%) 4 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 2/51 (3.9%) 6 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Tremor 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 6/304 (2%) 7 1/40 (2.5%) 1 1/21 (4.8%) 1 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 4/201 (2%) 4 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Psychiatric disorders
    Anxiety 0/4 (0%) 0 1/4 (25%) 1 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 1/62 (1.6%) 1 1/22 (4.5%) 1 16/304 (5.3%) 18 1/40 (2.5%) 2 1/21 (4.8%) 1 1/24 (4.2%) 1 2/51 (3.9%) 2 2/40 (5%) 2 0/31 (0%) 0 7/201 (3.5%) 7 1/20 (5%) 1 4/47 (8.5%) 4 1/20 (5%) 1 0/21 (0%) 0 8/62 (12.9%) 9 0/10 (0%) 0
    Confusional state 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 1/62 (1.6%) 1 0/22 (0%) 0 5/304 (1.6%) 5 2/40 (5%) 2 1/21 (4.8%) 1 1/24 (4.2%) 1 1/51 (2%) 1 0/40 (0%) 0 4/31 (12.9%) 4 8/201 (4%) 10 3/20 (15%) 3 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Depression 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/7 (0%) 0 1/21 (4.8%) 1 3/62 (4.8%) 3 1/22 (4.5%) 1 10/304 (3.3%) 10 1/40 (2.5%) 2 1/21 (4.8%) 1 1/24 (4.2%) 1 3/51 (5.9%) 3 0/40 (0%) 0 0/31 (0%) 0 8/201 (4%) 8 0/20 (0%) 0 2/47 (4.3%) 2 1/20 (5%) 1 1/21 (4.8%) 1 2/62 (3.2%) 2 0/10 (0%) 0
    Insomnia 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/6 (0%) 0 0/7 (0%) 0 1/21 (4.8%) 1 3/62 (4.8%) 4 2/22 (9.1%) 3 24/304 (7.9%) 26 7/40 (17.5%) 7 1/21 (4.8%) 4 2/24 (8.3%) 6 13/51 (25.5%) 25 2/40 (5%) 2 1/31 (3.2%) 1 20/201 (10%) 22 2/20 (10%) 2 4/47 (8.5%) 4 0/20 (0%) 0 3/21 (14.3%) 3 7/62 (11.3%) 10 0/10 (0%) 0
    Renal and urinary disorders
    Acute kidney injury 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 1/21 (4.8%) 1 0/62 (0%) 0 0/22 (0%) 0 3/304 (1%) 3 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 1/51 (2%) 1 0/40 (0%) 0 0/31 (0%) 0 8/201 (4%) 14 0/20 (0%) 0 2/47 (4.3%) 2 0/20 (0%) 0 1/21 (4.8%) 1 5/62 (8.1%) 5 0/10 (0%) 0
    Dysuria 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 1/62 (1.6%) 1 0/22 (0%) 0 2/304 (0.7%) 2 1/40 (2.5%) 1 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 1/40 (2.5%) 1 0/31 (0%) 0 6/201 (3%) 6 0/20 (0%) 0 1/47 (2.1%) 1 0/20 (0%) 0 2/21 (9.5%) 2 2/62 (3.2%) 2 1/10 (10%) 1
    Haematuria 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 1/62 (1.6%) 1 1/22 (4.5%) 2 1/304 (0.3%) 1 2/40 (5%) 2 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 18/201 (9%) 28 0/20 (0%) 0 3/47 (6.4%) 3 0/20 (0%) 0 1/21 (4.8%) 1 2/62 (3.2%) 4 0/10 (0%) 0
    Nocturia 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 1/40 (2.5%) 1 1/21 (4.8%) 1 0/24 (0%) 0 1/51 (2%) 1 0/40 (0%) 0 0/31 (0%) 0 1/201 (0.5%) 1 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 1/10 (10%) 1
    Pollakiuria 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 2/304 (0.7%) 2 2/40 (5%) 2 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 1/31 (3.2%) 1 3/201 (1.5%) 3 0/20 (0%) 0 1/47 (2.1%) 1 0/20 (0%) 0 1/21 (4.8%) 1 1/62 (1.6%) 1 0/10 (0%) 0
    Polyuria 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 1/10 (10%) 1
    Proteinuria 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 1/62 (1.6%) 1 0/22 (0%) 0 9/304 (3%) 11 2/40 (5%) 3 1/21 (4.8%) 3 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 4/201 (2%) 4 0/20 (0%) 0 3/47 (6.4%) 4 0/20 (0%) 0 2/21 (9.5%) 3 1/62 (1.6%) 2 0/10 (0%) 0
    Urinary incontinence 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 1/22 (4.5%) 1 3/304 (1%) 3 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 5/201 (2.5%) 5 2/20 (10%) 2 1/47 (2.1%) 1 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Urinary tract pain 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 2/22 (9.1%) 2 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 1/201 (0.5%) 1 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Reproductive system and breast disorders
    Pelvic pain 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 2/40 (5%) 3 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 1/31 (3.2%) 1 4/201 (2%) 5 0/20 (0%) 0 2/47 (4.3%) 2 0/20 (0%) 0 0/21 (0%) 0 1/62 (1.6%) 1 0/10 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Atelectasis 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 1/304 (0.3%) 1 2/40 (5%) 2 0/21 (0%) 0 0/24 (0%) 0 1/51 (2%) 1 0/40 (0%) 0 0/31 (0%) 0 1/201 (0.5%) 1 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Cough 0/4 (0%) 0 1/4 (25%) 1 0/3 (0%) 0 1/3 (33.3%) 1 1/6 (16.7%) 1 4/7 (57.1%) 7 2/21 (9.5%) 2 9/62 (14.5%) 11 2/22 (9.1%) 2 77/304 (25.3%) 102 7/40 (17.5%) 8 4/21 (19%) 4 5/24 (20.8%) 6 12/51 (23.5%) 15 5/40 (12.5%) 5 8/31 (25.8%) 10 24/201 (11.9%) 27 2/20 (10%) 2 1/47 (2.1%) 2 2/20 (10%) 2 6/21 (28.6%) 7 10/62 (16.1%) 13 2/10 (20%) 4
    Dysphonia 0/4 (0%) 0 1/4 (25%) 1 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 2/21 (9.5%) 2 2/62 (3.2%) 2 2/22 (9.1%) 2 13/304 (4.3%) 15 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 1/51 (2%) 2 1/40 (2.5%) 1 2/31 (6.5%) 2 4/201 (2%) 4 0/20 (0%) 0 0/47 (0%) 0 1/20 (5%) 1 1/21 (4.8%) 1 3/62 (4.8%) 3 0/10 (0%) 0
    Dyspnoea 1/4 (25%) 1 1/4 (25%) 1 0/3 (0%) 0 1/3 (33.3%) 1 1/6 (16.7%) 1 3/7 (42.9%) 4 2/21 (9.5%) 2 15/62 (24.2%) 21 5/22 (22.7%) 5 75/304 (24.7%) 100 8/40 (20%) 10 2/21 (9.5%) 2 6/24 (25%) 6 17/51 (33.3%) 22 10/40 (25%) 14 9/31 (29%) 10 27/201 (13.4%) 35 1/20 (5%) 1 9/47 (19.1%) 10 5/20 (25%) 5 3/21 (14.3%) 3 5/62 (8.1%) 5 2/10 (20%) 3
    Dyspnoea exertional 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/7 (0%) 0 0/21 (0%) 0 2/62 (3.2%) 3 0/22 (0%) 0 8/304 (2.6%) 9 1/40 (2.5%) 1 0/21 (0%) 0 0/24 (0%) 0 1/51 (2%) 1 1/40 (2.5%) 1 1/31 (3.2%) 1 4/201 (2%) 4 0/20 (0%) 0 3/47 (6.4%) 4 1/20 (5%) 2 1/21 (4.8%) 1 0/62 (0%) 0 0/10 (0%) 0
    Haemoptysis 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/6 (0%) 0 0/7 (0%) 0 1/21 (4.8%) 1 4/62 (6.5%) 4 0/22 (0%) 0 24/304 (7.9%) 29 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 1/51 (2%) 1 0/40 (0%) 0 0/31 (0%) 0 8/201 (4%) 10 0/20 (0%) 0 1/47 (2.1%) 2 0/20 (0%) 0 1/21 (4.8%) 1 1/62 (1.6%) 1 0/10 (0%) 0
    Hiccups 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 1/62 (1.6%) 1 0/22 (0%) 0 3/304 (1%) 4 2/40 (5%) 2 0/21 (0%) 0 0/24 (0%) 0 2/51 (3.9%) 8 0/40 (0%) 0 0/31 (0%) 0 3/201 (1.5%) 3 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Nasal congestion 1/4 (25%) 1 0/4 (0%) 0 2/3 (66.7%) 2 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 3/62 (4.8%) 3 1/22 (4.5%) 1 10/304 (3.3%) 13 0/40 (0%) 0 1/21 (4.8%) 1 3/24 (12.5%) 4 4/51 (7.8%) 4 0/40 (0%) 0 0/31 (0%) 0 4/201 (2%) 4 0/20 (0%) 0 2/47 (4.3%) 2 1/20 (5%) 1 1/21 (4.8%) 2 4/62 (6.5%) 9 1/10 (10%) 1
    Oropharyngeal pain 0/4 (0%) 0 0/4 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 7/62 (11.3%) 8 0/22 (0%) 0 17/304 (5.6%) 20 0/40 (0%) 0 1/21 (4.8%) 1 0/24 (0%) 0 2/51 (3.9%) 2 1/40 (2.5%) 1 0/31 (0%) 0 9/201 (4.5%) 9 0/20 (0%) 0 2/47 (4.3%) 2 0/20 (0%) 0 1/21 (4.8%) 1 3/62 (4.8%) 3 2/10 (20%) 2
    Pleural effusion 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 1/21 (4.8%) 1 5/62 (8.1%) 5 1/22 (4.5%) 2 14/304 (4.6%) 19 2/40 (5%) 2 0/21 (0%) 0 0/24 (0%) 0 2/51 (3.9%) 2 1/40 (2.5%) 1 2/31 (6.5%) 2 2/201 (1%) 2 0/20 (0%) 0 4/47 (8.5%) 5 2/20 (10%) 2 1/21 (4.8%) 1 1/62 (1.6%) 1 0/10 (0%) 0
    Pleuritic pain 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 1/21 (4.8%) 1 2/62 (3.2%) 2 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 2/201 (1%) 2 0/20 (0%) 0 0/47 (0%) 0 2/20 (10%) 2 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Pneumonitis 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 3/62 (4.8%) 3 0/22 (0%) 0 6/304 (2%) 8 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 1/51 (2%) 1 1/40 (2.5%) 1 1/31 (3.2%) 1 1/201 (0.5%) 1 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 1/10 (10%) 1
    Pneumothorax 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 1/7 (14.3%) 1 0/21 (0%) 0 2/62 (3.2%) 2 0/22 (0%) 0 5/304 (1.6%) 5 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 1/40 (2.5%) 1 0/31 (0%) 0 1/201 (0.5%) 1 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Productive cough 0/4 (0%) 0 0/4 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 1/21 (4.8%) 1 2/62 (3.2%) 2 0/22 (0%) 0 20/304 (6.6%) 23 1/40 (2.5%) 1 0/21 (0%) 0 0/24 (0%) 0 1/51 (2%) 1 0/40 (0%) 0 1/31 (3.2%) 1 10/201 (5%) 13 0/20 (0%) 0 2/47 (4.3%) 2 0/20 (0%) 0 0/21 (0%) 0 1/62 (1.6%) 1 0/10 (0%) 0
    Respiratory distress 0/4 (0%) 0 1/4 (25%) 1 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 1/22 (4.5%) 1 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 1/21 (4.8%) 2 0/62 (0%) 0 0/10 (0%) 0
    Rhinorrhoea 0/4 (0%) 0 0/4 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/6 (0%) 0 2/7 (28.6%) 2 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 4/304 (1.3%) 5 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 1/51 (2%) 1 0/40 (0%) 0 3/31 (9.7%) 3 3/201 (1.5%) 4 0/20 (0%) 0 1/47 (2.1%) 1 0/20 (0%) 0 0/21 (0%) 0 1/62 (1.6%) 1 0/10 (0%) 0
    Sinus congestion 1/4 (25%) 1 1/4 (25%) 1 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 3/304 (1%) 3 2/40 (5%) 2 1/21 (4.8%) 1 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 2/201 (1%) 2 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Sneezing 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 1/304 (0.3%) 1 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 1/40 (2.5%) 1 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 1/47 (2.1%) 1 0/20 (0%) 0 0/21 (0%) 0 1/62 (1.6%) 1 1/10 (10%) 1
    Upper-airway cough syndrome 0/4 (0%) 0 0/4 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 8/304 (2.6%) 8 0/40 (0%) 0 2/21 (9.5%) 2 0/24 (0%) 0 0/51 (0%) 0 1/40 (2.5%) 1 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 1/47 (2.1%) 1 0/20 (0%) 0 0/21 (0%) 0 1/62 (1.6%) 1 0/10 (0%) 0
    Wheezing 0/4 (0%) 0 1/4 (25%) 1 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 1/7 (14.3%) 1 0/21 (0%) 0 2/62 (3.2%) 2 1/22 (4.5%) 1 15/304 (4.9%) 17 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 3/201 (1.5%) 4 1/20 (5%) 1 2/47 (4.3%) 2 1/20 (5%) 1 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Skin and subcutaneous tissue disorders
    Acne 0/4 (0%) 0 1/4 (25%) 1 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 1/21 (4.8%) 1 0/62 (0%) 0 0/22 (0%) 0 1/304 (0.3%) 1 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Dermatitis acneiform 0/4 (0%) 0 0/4 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 1/51 (2%) 1 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Dry skin 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 2/21 (9.5%) 2 3/62 (4.8%) 3 1/22 (4.5%) 1 14/304 (4.6%) 15 0/40 (0%) 0 0/21 (0%) 0 2/24 (8.3%) 2 2/51 (3.9%) 2 2/40 (5%) 3 2/31 (6.5%) 2 7/201 (3.5%) 7 0/20 (0%) 0 3/47 (6.4%) 3 0/20 (0%) 0 1/21 (4.8%) 1 3/62 (4.8%) 3 1/10 (10%) 1
    Erythema 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 1/7 (14.3%) 1 0/21 (0%) 0 6/62 (9.7%) 7 0/22 (0%) 0 6/304 (2%) 6 1/40 (2.5%) 1 0/21 (0%) 0 1/24 (4.2%) 1 1/51 (2%) 4 2/40 (5%) 2 0/31 (0%) 0 3/201 (1.5%) 4 0/20 (0%) 0 1/47 (2.1%) 1 0/20 (0%) 0 0/21 (0%) 0 2/62 (3.2%) 2 0/10 (0%) 0
    Exfoliative rash 1/4 (25%) 2 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Hyperhidrosis 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 1/21 (4.8%) 1 1/62 (1.6%) 1 1/22 (4.5%) 2 5/304 (1.6%) 5 0/40 (0%) 0 0/21 (0%) 0 2/24 (8.3%) 2 5/51 (9.8%) 15 1/40 (2.5%) 1 2/31 (6.5%) 2 3/201 (1.5%) 3 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 1/21 (4.8%) 1 0/62 (0%) 0 0/10 (0%) 0
    Night sweats 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 8/304 (2.6%) 8 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 1/31 (3.2%) 1 7/201 (3.5%) 9 0/20 (0%) 0 1/47 (2.1%) 1 2/20 (10%) 2 0/21 (0%) 0 3/62 (4.8%) 3 0/10 (0%) 0
    Pemphigoid 0/4 (0%) 0 0/4 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 0/304 (0%) 0 0/40 (0%) 0 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 0/201 (0%) 0 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Petechiae 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 2/304 (0.7%) 2 1/40 (2.5%) 1 1/21 (4.8%) 1 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 1/201 (0.5%) 1 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Pruritus 0/4 (0%) 0 0/4 (0%) 0 1/3 (33.3%) 4 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 3/21 (14.3%) 4 5/62 (8.1%) 5 2/22 (9.1%) 3 35/304 (11.5%) 49 16/40 (40%) 20 5/21 (23.8%) 7 4/24 (16.7%) 4 6/51 (11.8%) 8 5/40 (12.5%) 6 5/31 (16.1%) 8 15/201 (7.5%) 20 0/20 (0%) 0 7/47 (14.9%) 10 3/20 (15%) 3 0/21 (0%) 0 10/62 (16.1%) 12 2/10 (20%) 3
    Rash 0/4 (0%) 0 2/4 (50%) 4 2/3 (66.7%) 3 0/3 (0%) 0 1/6 (16.7%) 1 1/7 (14.3%) 1 1/21 (4.8%) 1 6/62 (9.7%) 6 2/22 (9.1%) 2 37/304 (12.2%) 54 5/40 (12.5%) 7 4/21 (19%) 7 7/24 (29.2%) 12 9/51 (17.6%) 13 1/40 (2.5%) 1 4/31 (12.9%) 6 23/201 (11.4%) 28 1/20 (5%) 1 2/47 (4.3%) 2 1/20 (5%) 1 0/21 (0%) 0 3/62 (4.8%) 3 2/10 (20%) 2
    Rash maculo-papular 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 1/21 (4.8%) 1 4/62 (6.5%) 6 1/22 (4.5%) 1 7/304 (2.3%) 13 1/40 (2.5%) 1 1/21 (4.8%) 2 1/24 (4.2%) 1 0/51 (0%) 0 0/40 (0%) 0 1/31 (3.2%) 1 5/201 (2.5%) 13 0/20 (0%) 0 1/47 (2.1%) 1 0/20 (0%) 0 2/21 (9.5%) 2 5/62 (8.1%) 5 0/10 (0%) 0
    Vitiligo 0/4 (0%) 0 0/4 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/6 (0%) 0 1/7 (14.3%) 1 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 1/304 (0.3%) 1 0/40 (0%) 0 2/21 (9.5%) 2 1/24 (4.2%) 1 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 2/201 (1%) 2 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Vascular disorders
    Deep vein thrombosis 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 1/7 (14.3%) 1 1/21 (4.8%) 1 0/62 (0%) 0 1/22 (4.5%) 1 3/304 (1%) 3 1/40 (2.5%) 1 0/21 (0%) 0 0/24 (0%) 0 0/51 (0%) 0 0/40 (0%) 0 0/31 (0%) 0 3/201 (1.5%) 3 0/20 (0%) 0 0/47 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/10 (0%) 0
    Hot flush 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 1/7 (14.3%) 1 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 4/304 (1.3%) 4 2/40 (5%) 2 1/21 (4.8%) 1 0/24 (0%) 0 1/51 (2%) 1 0/40 (0%) 0 0/31 (0%) 0 3/201 (1.5%) 3 0/20 (0%) 0 1/47 (2.1%) 1 3/20 (15%) 3 0/21 (0%) 0 1/62 (1.6%) 1 0/10 (0%) 0
    Hypertension 0/4 (0%) 0 1/4 (25%) 1 0/3 (0%) 0 1/3 (33.3%) 3 0/6 (0%) 0 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 11/304 (3.6%) 16 1/40 (2.5%) 1 1/21 (4.8%) 1 0/24 (0%) 0 2/51 (3.9%) 2 1/40 (2.5%) 2 0/31 (0%) 0 7/201 (3.5%) 13 3/20 (15%) 3 0/47 (0%) 0 1/20 (5%) 1 1/21 (4.8%) 1 2/62 (3.2%) 2 0/10 (0%) 0
    Hypotension 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/7 (0%) 0 1/21 (4.8%) 1 1/62 (1.6%) 1 0/22 (0%) 0 12/304 (3.9%) 12 1/40 (2.5%) 1 0/21 (0%) 0 0/24 (0%) 0 1/51 (2%) 1 0/40 (0%) 0 0/31 (0%) 0 10/201 (5%) 12 0/20 (0%) 0 1/47 (2.1%) 1 0/20 (0%) 0 2/21 (9.5%) 3 3/62 (4.8%) 3 0/10 (0%) 0
    Lymphoedema 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/7 (0%) 0 0/21 (0%) 0 0/62 (0%) 0 0/22 (0%) 0 1/304 (0.3%) 1 0/40 (0%) 0 1/21 (4.8%) 1 0/24 (0%) 0 1/51 (2%) 1 0/40 (0%) 0 0/31 (0%) 0 1/201 (0.5%) 2 0/20 (0%) 0 1/47 (2.1%) 1 0/20 (0%) 0 0/21 (0%) 0 1/62 (1.6%) 2 0/10 (0%) 0

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    MedImmune has 60 days to review results communications prior to public release and may delete information that compromises ongoing studies or is considered proprietary. This restriction is not intended to compromise the objective scientific integrity of the manuscript, it being understood that results shall be published regardless of outcome.

    Results Point of Contact

    Name/Title Ashok Gupta
    Organization MedImmune, LLC
    Phone +13013981287
    Email information.center@astrazeneca.com
    Responsible Party:
    MedImmune LLC
    ClinicalTrials.gov Identifier:
    NCT01693562
    Other Study ID Numbers:
    • CD-ON-MEDI4736-1108
    First Posted:
    Sep 26, 2012
    Last Update Posted:
    May 13, 2021
    Last Verified:
    Apr 1, 2021