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A Phase 1/2, Open-label Study to Evaluate the Safety and Antitumor Activity of MEDI0680 (AMP-514) in Combination With Durvalumab Versus Nivolumab Monotherapy in Participants With Select Advanced Malignancies

Sponsor
MedImmune LLC (Industry)
Overall Status
Completed
CT.gov ID
NCT02118337
Collaborator
(none)
97
Enrollment
27
Locations
9
Arms
69.9
Actual Duration (Months)
3.6
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

To evaluate the Safety and Antitumor Activity of MEDI0680 (AMP-514) in Combination with Durvalumab versus Nivolumab Monotherapy in Participants with Select Advanced Malignancies.

Condition or Disease Intervention/Treatment Phase
  • Biological: MEDI0680
  • Biological: Durvalumab
  • Biological: Nivolumab
 Phase 1/Phase 2

Detailed Description

This is a multicenter, open-label, Phase 1/2 study to evaluate the safety, tolerability, PK, immunogenicity, and antitumor activity of MEDI0680 in combination with durvalumab or nivolumab monotherapy in adult immunotherapy-naïve participants with selected advanced malignancies.

Study Design

Study Type:
Interventional
Actual Enrollment :
97 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 1/2, Open-label Study to Evaluate the Safety and Antitumor Activity of MEDI0680 (AMP-514) in Combination With Durvalumab Versus Nivolumab Monotherapy in Subjects With Select Advanced Malignancies
Actual Study Start Date :
May 19, 2014
Actual Primary Completion Date :
Mar 17, 2020
Actual Study Completion Date :
Mar 17, 2020

Arms and Interventions

Arm Intervention/Treatment
Experimental: MEDI0680 0.1 mg/kg + Durvalumab 3 mg/kg

Participants in dose-escalation phase will receive IV infusion of MEDI0680 0.1 mg/kg and durvalumab 3 mg/kg every 2 weeks (Q2W) for up to 12 months.

Biological: MEDI0680
Participants will receive IV infusion of MEDI0680 0.1 or 0.5 or 2.5 or 10 or 20 mg/kg Q2W in dose-escalation phase and 20 mg/kg Q2W in dose-expansion phase.
Other Names:
  • AMP-514

    • Biological: Durvalumab
    Participants will receive IV infusion of durvalumab 3 and 10 mg Q2W in dose-escalation phase and 750 mg Q2W in dose-expansion phase.
    Experimental: MEDI0680 0.1 mg/kg + Durvalumab 10 mg

    Participants in dose-escalation phase will receive IV infusion of MEDI0680 0.1 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months.

    Biological: MEDI0680
    Participants will receive IV infusion of MEDI0680 0.1 or 0.5 or 2.5 or 10 or 20 mg/kg Q2W in dose-escalation phase and 20 mg/kg Q2W in dose-expansion phase.
    Other Names:
  • AMP-514

    • Biological: Durvalumab
    Participants will receive IV infusion of durvalumab 3 and 10 mg Q2W in dose-escalation phase and 750 mg Q2W in dose-expansion phase.
    Experimental: MEDI0680 0.5 mg/kg + Durvalumab 10 mg

    Participants in dose-escalation phase will receive IV infusion of MEDI0680 0.5 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months.

    Biological: MEDI0680
    Participants will receive IV infusion of MEDI0680 0.1 or 0.5 or 2.5 or 10 or 20 mg/kg Q2W in dose-escalation phase and 20 mg/kg Q2W in dose-expansion phase.
    Other Names:
  • AMP-514

    • Biological: Durvalumab
    Participants will receive IV infusion of durvalumab 3 and 10 mg Q2W in dose-escalation phase and 750 mg Q2W in dose-expansion phase.
    Experimental: MEDI0680 2.5 mg/kg + Durvalumab 10 mg

    Participants in dose-escalation phase will receive IV infusion of MEDI0680 2.5 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months.

    Biological: MEDI0680
    Participants will receive IV infusion of MEDI0680 0.1 or 0.5 or 2.5 or 10 or 20 mg/kg Q2W in dose-escalation phase and 20 mg/kg Q2W in dose-expansion phase.
    Other Names:
  • AMP-514

    • Biological: Durvalumab
    Participants will receive IV infusion of durvalumab 3 and 10 mg Q2W in dose-escalation phase and 750 mg Q2W in dose-expansion phase.
    Experimental: MEDI0680 10 mg/kg + Durvalumab 10 mg

    Participants in dose-escalation phase will receive IV infusion of MEDI0680 10 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months.

    Biological: MEDI0680
    Participants will receive IV infusion of MEDI0680 0.1 or 0.5 or 2.5 or 10 or 20 mg/kg Q2W in dose-escalation phase and 20 mg/kg Q2W in dose-expansion phase.
    Other Names:
  • AMP-514

    • Biological: Durvalumab
    Participants will receive IV infusion of durvalumab 3 and 10 mg Q2W in dose-escalation phase and 750 mg Q2W in dose-expansion phase.
    Experimental: MEDI0680 20 mg/kg + Durvalumab 10 mg

    Participants in dose-escalation phase will receive IV infusion of MEDI0680 20 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months.

    Biological: MEDI0680
    Participants will receive IV infusion of MEDI0680 0.1 or 0.5 or 2.5 or 10 or 20 mg/kg Q2W in dose-escalation phase and 20 mg/kg Q2W in dose-expansion phase.
    Other Names:
  • AMP-514

    • Biological: Durvalumab
    Participants will receive IV infusion of durvalumab 3 and 10 mg Q2W in dose-escalation phase and 750 mg Q2W in dose-expansion phase.
    Experimental: MEDI0680 20 mg/kg

    Participants in dose-expansion phase will receive IV infusion of MEDI0680 20 mg/kg Q2W until unacceptable toxicity, confirmed disease progression, development of other reason for treatment discontinuation, or for a maximum of 2 years, whichever occurred first.

    Biological: MEDI0680
    Participants will receive IV infusion of MEDI0680 0.1 or 0.5 or 2.5 or 10 or 20 mg/kg Q2W in dose-escalation phase and 20 mg/kg Q2W in dose-expansion phase.
    Other Names:
  • AMP-514

    		•
    Experimental: MEDI0680 20 mg/kg + Durvalumab 750 mg

    Participants in dose-expansion phase will receive IV infusion of MEDI0680 20 mg/kg and durvalumab 750 mg/kg Q2W until unacceptable toxicity, confirmed disease progression, development of other reason for treatment discontinuation, or for a maximum of 2 years, whichever occurred first.

    Biological: MEDI0680
    Participants will receive IV infusion of MEDI0680 0.1 or 0.5 or 2.5 or 10 or 20 mg/kg Q2W in dose-escalation phase and 20 mg/kg Q2W in dose-expansion phase.
    Other Names:
  • AMP-514

    • Biological: Durvalumab
    Participants will receive IV infusion of durvalumab 3 and 10 mg Q2W in dose-escalation phase and 750 mg Q2W in dose-expansion phase.
    Active Comparator: Nivolumab 240 mg

    Participants in dose-expansion phase will receive IV infusion of nivolumab 240 mg Q2W until unacceptable toxicity, confirmed disease progression, development of other reason for treatment discontinuation, or for a maximum of 2 years, whichever occurred first.

    Biological: Nivolumab
    Participants will receive IV infusion of nivolumab 240 mg Q2W in dose-expansion phase.

    Outcome Measures

    Primary Outcome Measures

    1. Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) in Dose-escalation Phase [Day 1 through 90 days post end of treatment (approximately 5 years 10 months)]

      An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An 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.

    2. Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase [Day 1 through 90 days post end of treatment (approximately 5 years 10 months)]

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

    3. Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAES in Dose-escalation Phase [Day 1 through 90 days post end of treatment (approximately 5 years 10 months)]

      Number of participants in dose-escalation phase with abnormal vital signs reported as TEAEs are reported. Abnormal vital signs is defined as any abnormal finding in the vital sign parameters (blood pressure, heart rate, body temperature, and respiratory rate). Abnormal physical examination findings are defined as any abnormal finding in the following body systems: head and neck, respiratory, cardiovascular, gastrointestinal, urogenital, musculoskeletal, neurological, psychiatric, dermatological, hematologic/lymphatic, and endocrine systems, and weight.

    4. Number of Participants With Abnormal Electrocardiograms (ECGs) Reported as TEAEs in Dose-escalation Phase [Day 1 through 90 days post end of treatment (approximately 5 years 10 months)]

      Number of participants in dose-escalation phase with abnormal ECG parameters reported as TEAEs are reported.

    5. Objective Response Rate (ORR) Based on Investigator-assessed Response Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) in Dose-expansion Phase [From baseline (Day -42 to Day -1) through disease progression or end of treatment (approximately 5 years 10 months)]

      The ORR is defined as best overall response of confirmed complete response (CR) or confirmed partial response (PR) based on RECIST v1.1. 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 non-target lesion. A confirmed CR or PR is defined as 2 CRs or 2 PRs that were separated by at least 4 weeks with no evidence of progression in-between.

    Secondary Outcome Measures

    1. Best Overall Response (BOR) Based on Investigator-assessed RECIST v1.1 in Dose-expansion Phase [From baseline (Day -42 to Day -1) through disease progression or end of treatment (approximately 5 years 10 months)]

      The BOR includes CR, PR, stable disease (SD), progressive disease (PD), and non-evaluable (NE) based on RECIST v1.1. 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% decrease 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.

    2. Disease Control Rate (DCR) Based on Investigator-assessed RECIST v1.1 in Dose-expansion Phase [From baseline (Day -42 to Day -1) through disease progression or end of treatment (approximately 5 years 10 months)]

      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 4 weeks 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) that were separated by at least 4 weeks 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. The DCR at >= 8 weeks and >=24 weeks are reported.

    3. Time to Response (TTR) Based on Investigator-assessed RECIST v1.1 in Dose-expansion Phase [From baseline (Day -42 to Day -1) through disease progression or end of treatment (approximately 5 years 10 months)]

      The TTR is defined as the time from the first dose of treatment until the first documentation of a subsequently confirmed OR (confirmed CR or confirmed PR) 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 4 weeks 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) that were separated by at least 4 weeks with no evidence of progression in-between. The TTR was estimated using Kaplan-Meier method.

    4. Duration of Response (DoR) Based on Investigator-assessed RECIST v1.1 in Dose-expansion Phase [From baseline (Day -42 to Day -1) through disease progression or end of treatment (approximately 5 years 10 months)]

      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 4 weeks 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) that were separated by at least 4 weeks with no evidence of progression in-between. The PD is defined at least 20% decrease in the sum of diameters of target lesions (compared to baseline) and/or new lesion. The DoR was estimated using Kaplan-Meier method.

    5. Progression Free Survival (PFS) Based on Investigator-assessed RECIST v1.1 in Dose-expansion Phase [From baseline (Day -42 to Day -1) through disease progression or end of treatment (approximately 5 years 10 months)]

      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 PFS was estimated using Kaplan-Meier method.

    6. Overall Survival in Dose-expansion Phase [From baseline (Day -42 to Day -1) through disease progression or end of treatment (approximately 5 years 10 months)]

      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.

    7. BOR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase [From baseline (Day -42 to Day -1) through disease progression or EOT (approximately 12 months for each participant)]

      The BOR includes CR, PR, SD, PD, and NE per Modified RECIST v1.1. 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% decrease 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.

    8. ORR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase [From baseline (Day -42 to Day -1) through disease progression or EOT (approximately 12 months for each participant)]

      The ORR is defined as best overall response of confirmed CR or confirmed PR based on modified RECIST v1.1. 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 non-target lesion. A confirmed CR or PR is defined as 2 CRs or 2 PRs that were separated by at least 4 weeks with no evidence of progression in-between.

    9. DCR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase [From baseline (Day -42 to Day -1) through disease progression or EOT (approximately 12 months for each participant)]

      The DCR is defined as a BOR of confirmed CR, confirmed PR, or SD based on modified 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 4 weeks 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) that were separated by at least 4 weeks 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. The DCR at >= 8 weeks and >=24 weeks are reported.

    10. TTR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase [From baseline (Day -42 to Day -1) through disease progression or EOT (approximately 12 months for each participant)]

      The TTR is defined as the time from the first dose of treatment until the first documentation of a subsequently confirmed OR (confirmed CR or confirmed PR) based on modified 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 4 weeks 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) that were separated by at least 4 weeks with no evidence of progression in-between. The TTR was estimated using Kaplan-Meier method.

    11. DoR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase [From baseline (Day -42 to Day -1) through disease progression or EOT (approximately 12 months for each participant)]

      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 modified 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 4 weeks 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) that were separated by at least 4 weeks with no evidence of progression in-between. The PD is defined at least 20% decrease in the sum of diameters of target lesions (compared to baseline) and/or new lesion. The DoR was estimated using Kaplan-Meier method.

    12. PFS Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase [From baseline (Day -42 to Day -1) through disease progression or EOT (approximately 12 months for each participant)]

      The PFS is defined as the time from the start of study treatment until the first documentation of disease progression based on modified RECIST v1.1 or death due to any cause, whichever occurred first. The PFS was estimated using Kaplan-Meier method.

    13. OS in Dose-escalation Phase [From baseline (Day -42 to Day -1) through disease progression or EOT (approximately 12 months for each participant)]

      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.

    14. Number of Participants With TEAEs and TESAEs in Dose-expansion Phase [Day 1 through 90 days post end of treatment (approximately 5 years 10 months)]

      An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An 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.

    15. Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase [Day 1 through 90 days post end of treatment (approximately 5 years 10 months)]

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

    16. Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Dose-expansion Phase [Day 1 through 90 days post end of treatment (approximately 5 years 10 months)]

      Number of participants in dose-expansion phase with abnormal vital signs reported as TEAEs are reported. Abnormal vital signs is defined as any abnormal finding in the vital sign parameters (blood pressure, heart rate, body temperature, and respiratory rate). Abnormal physical examination findings are defined as any abnormal finding in the following body systems: head and neck, respiratory, cardiovascular, gastrointestinal, urogenital, musculoskeletal, neurological, psychiatric, dermatological, hematologic/lymphatic, and endocrine systems, and weight.

    17. Number of Participants With Abnormal ECGs Reported as TEAEs in Dose-expansion Phase [Day 1 through 90 days post end of treatment (approximately 5 years 10 months)]

      Number of participants in dose-expansion phase with abnormal ECG parameters reported as TEAEs are reported.

    18. Antitumor Activity of MEDI0680 and Durvalumab Versus Nivolumab Monotherapy in Immunotherapy-Naïve Participants With Advanced or Metastatic Clear-cell Renal Cell Carcinoma (ccRCC) Based on Blinded Independent Central Review (BICR) in Dose-expansion Phase [From baseline (Day -42 to Day -1) through disease progression or end of treatment (approximately 5 years 10 months)]

    19. Percent Change From Baseline in Tumor Size in Dose-escalation Phase (Based on Investigator-assessed Modified RECIST v1.1) and Dose-expansion Phase (Based on Investigator-assessed RECIST v1.1) [From baseline (Day -42 to Day -1) through disease progression or EOT (approximately 12 months for each participant for dose-escalation phase and approximately 5 years 10 months for dose-expansion phase)]

    20. Serum Concentration of MEDI0680 in Dose-escalation and Dose-expansion Phases [Pre-dose and end of infusion on Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1]

      Serum concentration of MEDI0680 were assessed using parameters Cmin (pre-dose) and Cmax (end of infusion), where Cmin was trough concentration and Cmax was peak concentration.

    21. Serum Concentration of Durvalumab in Dose-escalation and Dose-expansion Phases [Pre-dose and end of infusion on Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1]

      Serum concentration of durvalumab were assessed using parameters Cmin (pre-dose) and Cmax (end of infusion), where Cmin was trough concentration and Cmax was peak concentration.

    22. Number of Participants With Positive Anti-drug Antibodies (ADA) to MEDI0680 in Dose-escalation and Dose-expansion Phases [Cycle 1 Day 1, Cycle 2 Day 1, Cycle 5 Day 1, Cycle 8 Day 1, Cycle 11 Day 1, 90 and 180 days post end of treatment (approximately 5 years and 10 months)]

      Number of participants with positive ADAs to MEDI0680 are reported. 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. Transient positive is defined as negative at last post-baseline assessment and positive at only one post-baseline assessment or at >=2 post-baseline assessments (with <16 weeks between first and last positive).

    23. Number of Participants With Positive ADA to Durvalumab in Dose-escalation and Dose-expansion Phases [Cycle 1 Day 1, Cycle 2 Day 1, Cycle 5 Day 1, Cycle 8 Day 1, Cycle 11 Day 1, 90 and 180 days post end of treatment (approximately 5 years and 10 months)]

      Number of participants with positive ADA to durvalumab are reported. 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. Transient positive is defined as negative at last post-baseline assessment and positive at only one post-baseline assessment or at >=2 post-baseline assessments (with <16 weeks between first and last positive).

    24. ORR for Participants With Programmed Cell Death Ligand 1 (PD-L1) Status Positive and Negative in Dose-expansion Phase [From baseline (Day -42 to Day -1) through disease progression or end of treatment (approximately 5 years 10 months)]

      ORR for participants with PD-L1 status positive and negative are reported. The ORR is defined as best overall response 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. The PR is defined as >= 30% decrease in the sum of diameters of target lesions (compared to baseline) and no new non-target lesion. A confirmed CR or PR is defined as 2 CRs or 2 PRs that were separated by at least 4 weeks with no evidence of progression in-between.

    Eligibility Criteria

    Criteria

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

    • Must be 18 years or older

    • Eastern Cooperative Oncology Group performance status of 0-1

    • Adequate organ function

    • At least 1 prior line of therapy

    Exclusion Criteria:

    • Concurrent enrollment in another clinical study, unless in follow-up period or it is an observational study

    • Concurrent chemotherapy, immunotherapy, biologic, or hormonal therapy for cancer treatment

    • Prior treatment with immunotherapy

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Research Site Los Angeles California United States 90025
    2 Research Site Tampa Florida United States 33612
    3 Research Site Overland Park Kansas United States 66209
    4 Research Site Louisville Kentucky United States 40202
    5 Research Site Rochester Minnesota United States 55905
    6 Research Site Hackensack New Jersey United States 07601
    7 Research Site New York New York United States 10065
    8 Research Site Cleveland Ohio United States 44195
    9 Research Site Oklahoma City Oklahoma United States 73104
    10 Research Site Portland Oregon United States 97213
    11 Research Site Hershey Pennsylvania United States 17033-0850
    12 Research Site Nashville Tennessee United States 37203
    13 Research Site Seattle Washington United States 98109
    14 Research Site East Bentleigh Australia 3165
    15 Research Site Frankston Australia 3199
    16 Research Site Toronto Ontario Canada M5G 2M9
    17 Research Site Montreal Quebec Canada H3T 1E2
    18 Research Site Bordeaux France 33075
    19 Research Site Dijon France 21079
    20 Research Site Marseille France 13009
    21 Research Site Paris Cedex 15 France 75908
    22 Research Site Villejuif France 94805
    23 Research Site Amsterdam Netherlands 1066 CX
    24 Research Site Groningen Netherlands 9713 GZ
    25 Research Site Cambridge United Kingdom CB2 0QQ
    26 Research Site Cardiff United Kingdom CF14 2TL
    27 Research Site Southampton United Kingdom SO16 6YD

    Sponsors and Collaborators

    • MedImmune LLC

    Investigators

    • Principal Investigator: Laura Chow, MD, University of Washington
    • Principal Investigator: Omid Hamid, MD, The Angeles Clinic
    • Principal Investigator: Jhanelle Gray, MD, Moffitt Cancer Center
    • Principal Investigator: Rachel Sanborn, MD, Providence Cancer Center
    • Principal Investigator: Mohamad Salkeni, MD, Mary Babb Randolph Cancer Center
    • Principal Investigator: Monika Joshi, MD, Penn State Hershey Cancer Institute
    • Principal Investigator: Robert Alter, MD, John Theurer Cancer Center
    • Principal Investigator: Raid Aljumaily, MD, Peggy Charles Stephenson Cancer Center
    • Principal Investigator: Jason Chesney, MD, Brown Cancer Center
    • Principal Investigator: Fernando Quevedo, MD, Mayo Clinic
    • Principal Investigator: Martin Voss, MD, Memorial Sloan Kettering Cancer Center
    • Principal Investigator: Johanna Bendell, SCRI Development Innovations, LLC
    • Principal Investigator: Elizabeth Henry, Loyola Univ. Medical Center
    • Principal Investigator: Lionel Lewis, Dartmouth-Hitchcock Medical Center
    • Principal Investigator: Brian Rini, The Cleveland Clinic
    • Principal Investigator: Peter Van Veldhuizen, Menorah Medical Center tour

    Study Documents (Full-Text)

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    MedImmune LLC
    ClinicalTrials.gov Identifier:
    NCT02118337
    Other Study ID Numbers:
    • D6020C00001
    First Posted:
    Apr 21, 2014
    Last Update Posted:
    Jun 1, 2021
    Last Verified:
    May 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Keywords provided by MedImmune LLC
    select advanced malignancies,
    kidney cancer,
    clear cell renal cell carcinoma
    Additional relevant MeSH terms:
    Neoplasms
    Carcinoma, Renal Cell
    Kidney Neoplasms
    Nivolumab
    Durvalumab

    Study Results

    Participant Flow

    Recruitment Details The study is conducted in Australia, Canada, Europe and the USA.
    Pre-assignment Detail
    Arm/Group Title MEDI0680 0.1 mg/kg + Durvalumab 3 mg MEDI0680 0.1 mg/kg + Durvalumab 10 mg MEDI0680 0.5 mg/kg + Durvalumab 10 mg MEDI0680 2.5 mg/kg + Durvalumab 10 mg MEDI0680 10 mg/kg + Durvalumab 10 mg MEDI0680 20 mg/kg + Durvalumab 10 mg MEDI0680 20 mg/kg MEDI0680 20 mg/kg + Durvalumab 750 mg Nivolumab 240 mg
    Arm/Group Description Participants in dose-escalation phase received IV infusion of MEDI0680 0.1 mg/kg and durvalumab 3 mg/kg every 2 weeks (Q2W) for up to 12 months. Participants in dose-escalation phase received IV infusion of MEDI0680 0.1 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months. Participants in dose-escalation phase received IV infusion of MEDI0680 0.5 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months. Participants in dose-escalation phase received IV infusion of MEDI0680 2.5 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months. Participants in dose-escalation phase received IV infusion of MEDI0680 10 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months. Participants in dose-escalation phase received IV infusion of MEDI0680 20 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months. Participants in dose-expansion phase received IV infusion of MEDI0680 20 mg/kg Q2W until unacceptable toxicity, confirmed disease progression, development of other reason for treatment discontinuation, or for a maximum of 2 years, whichever occurred first. Participants in dose-expansion phase received IV infusion of MEDI0680 20 mg/kg and durvalumab 750 mg/kg Q2W until unacceptable toxicity, confirmed disease progression, development of other reason for treatment discontinuation, or for a maximum of 2 years, whichever occurred first. Participants in dose-expansion phase received IV infusion of nivolumab 240 mg Q2W until unacceptable toxicity, confirmed disease progression, development of other reason for treatment discontinuation, or for a maximum of 2 years, whichever occurred first.
    Period Title: Overall Study
    STARTED 4 5 3 3 9 6 4 42 21
    COMPLETED 0 0 0 0 0 0 0 0 0
    NOT COMPLETED 4 5 3 3 9 6 4 42 21

    Baseline Characteristics

    Arm/Group Title MEDI0680 0.1 mg/kg + Durvalumab 3 mg MEDI0680 0.1 mg/kg + Durvalumab 10 mg MEDI0680 0.5 mg/kg + Durvalumab 10 mg MEDI0680 2.5 mg/kg + Durvalumab 10 mg MEDI0680 10 mg/kg + Durvalumab 10 mg MEDI0680 20 mg/kg + Durvalumab 10 mg MEDI0680 20 mg/kg MEDI0680 20 mg/kg + Durvalumab 750 mg Nivolumab 240 mg Total
    Arm/Group Description Participants in dose-escalation phase received IV infusion of MEDI0680 0.1 mg/kg and durvalumab 3 mg/kg Q2W for up to 12 months. Participants in dose-escalation phase received IV infusion of MEDI0680 0.1 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months. Participants in dose-escalation phase received IV infusion of MEDI0680 0.5 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months. Participants in dose-escalation phase received IV infusion of MEDI0680 2.5 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months. Participants in dose-escalation phase received IV infusion of MEDI0680 10 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months. Participants in dose-escalation phase received IV infusion of MEDI0680 20 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months. Participants in dose-expansion phase received IV infusion of MEDI0680 20 mg/kg Q2W until unacceptable toxicity, confirmed disease progression, development of other reason for treatment discontinuation, or for a maximum of 2 years, whichever occurred first. Participants in dose-expansion phase received IV infusion of MEDI0680 20 mg/kg and durvalumab 750 mg/kg Q2W until unacceptable toxicity, confirmed disease progression, development of other reason for treatment discontinuation, or for a maximum of 2 years, whichever occurred first. Participants in dose-expansion phase received IV infusion of nivolumab 240 mg Q2W until unacceptable toxicity, confirmed disease progression, development of other reason for treatment discontinuation, or for a maximum of 2 years, whichever occurred first. Total of all reporting groups
    Overall Participants 4 5 3 3 9 6 4 42 21 97
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    60.5
    (12.6)
    67.4
    (8.4)
    52.3
    (17.9)
    62.3
    (11.6)
    62.1
    (11.0)
    69.5
    (9.9)
    64.8
    (14.2)
    61.0
    (9.8)
    59.1
    (10.5)
    61.5
    (10.6)
    Sex: Female, Male (Count of Participants)
    Female
    1
    25%
    3
    60%
    1
    33.3%
    1
    33.3%
    5
    55.6%
    2
    33.3%
    1
    25%
    9
    21.4%
    6
    28.6%
    29
    29.9%
    Male
    3
    75%
    2
    40%
    2
    66.7%
    2
    66.7%
    4
    44.4%
    4
    66.7%
    3
    75%
    33
    78.6%
    15
    71.4%
    68
    70.1%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    1
    25%
    0
    0%
    1
    33.3%
    0
    0%
    2
    22.2%
    0
    0%
    0
    0%
    1
    2.4%
    1
    4.8%
    6
    6.2%
    Not Hispanic or Latino
    3
    75%
    5
    100%
    2
    66.7%
    2
    66.7%
    7
    77.8%
    6
    100%
    4
    100%
    40
    95.2%
    20
    95.2%
    89
    91.8%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    1
    33.3%
    0
    0%
    0
    0%
    0
    0%
    1
    2.4%
    0
    0%
    2
    2.1%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    25%
    0
    0%
    0
    0%
    1
    1%
    Asian
    0
    0%
    1
    20%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    2.4%
    0
    0%
    2
    2.1%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    11.1%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    1%
    Black or African American
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    3
    14.3%
    3
    3.1%
    White
    4
    100%
    4
    80%
    3
    100%
    2
    66.7%
    8
    88.9%
    6
    100%
    3
    75%
    34
    81%
    16
    76.2%
    80
    82.5%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    1
    33.3%
    0
    0%
    0
    0%
    0
    0%
    7
    16.7%
    2
    9.5%
    10
    10.3%

    Outcome Measures

    1. Primary Outcome
    Title Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) in Dose-escalation 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. An 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 Day 1 through 90 days post end of treatment (approximately 5 years 10 months)

    Outcome Measure Data

    Analysis Population Description
    As-treated population included those participants who received any study drug (MEDI0680, durvalumab, or nivolumab) and grouped according to actual treatment received.
    Arm/Group Title MEDI0680 0.1 mg/kg + Durvalumab 3 mg MEDI0680 0.1 mg/kg + Durvalumab 10 mg MEDI0680 0.5 mg/kg + Durvalumab 10 mg MEDI0680 2.5 mg/kg + Durvalumab 10 mg MEDI0680 10 mg/kg + Durvalumab 10 mg MEDI0680 20 mg/kg + Durvalumab 10 mg
    Arm/Group Description Participants in dose-escalation phase received IV infusion of MEDI0680 0.1 mg/kg and durvalumab 3 mg/kg every 2 weeks (Q2W) for up to 12 months. Participants in dose-escalation phase received IV infusion of MEDI0680 0.1 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months. Participants in dose-escalation phase received IV infusion of MEDI0680 0.5 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months. Participants in dose-escalation phase received IV infusion of MEDI0680 2.5 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months. Participants in dose-escalation phase received IV infusion of MEDI0680 10 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months. Participants in dose-escalation phase received IV infusion of MEDI0680 20 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months.
    Measure Participants 4 5 3 3 9 6
    Any TEAE
    4
    100%
    5
    100%
    3
    100%
    3
    100%
    9
    100%
    6
    100%
    Any TESAE
    1
    25%
    1
    20%
    1
    33.3%
    2
    66.7%
    6
    66.7%
    0
    0%
    2. Primary Outcome
    Title Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase
    Description Number of participants in dose-escalation phase with abnormal clinical laboratory parameters reported as TEAEs are reported. Abnormal clinical laboratory parameters are defined as any abnormal finding during analysis of serum chemistry, hematology, coagulation, and urine.
    Time Frame Day 1 through 90 days post end of treatment (approximately 5 years 10 months)

    Outcome Measure Data

    Analysis Population Description
    As-treated population included those participants who received any study drug (MEDI0680, durvalumab, or nivolumab) and grouped according to actual treatment received.
    Arm/Group Title MEDI0680 0.1 mg/kg + Durvalumab 3 mg MEDI0680 0.1 mg/kg + Durvalumab 10 mg MEDI0680 0.5 mg/kg + Durvalumab 10 mg MEDI0680 2.5 mg/kg + Durvalumab 10 mg MEDI0680 10 mg/kg + Durvalumab 10 mg MEDI0680 20 mg/kg + Durvalumab 10 mg
    Arm/Group Description Participants in dose-escalation phase received IV infusion of MEDI0680 0.1 mg/kg and durvalumab 3 mg/kg every 2 weeks (Q2W) for up to 12 months. Participants in dose-escalation phase received IV infusion of MEDI0680 0.1 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months. Participants in dose-escalation phase received IV infusion of MEDI0680 0.5 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months. Participants in dose-escalation phase received IV infusion of MEDI0680 2.5 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months. Participants in dose-escalation phase received IV infusion of MEDI0680 10 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months. Participants in dose-escalation phase received IV infusion of MEDI0680 20 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months.
    Measure Participants 4 5 3 3 9 6
    Anaemia
    0
    0%
    0
    0%
    1
    33.3%
    1
    33.3%
    3
    33.3%
    0
    0%
    Iron deficiency anaemia
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    11.1%
    0
    0%
    Leukocytosis
    1
    25%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Lymphopenia
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    11.1%
    0
    0%
    Activated partial thromboplastin time prolonged
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    16.7%
    Blood fibrinogen decreased
    1
    25%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    16.7%
    International normalized ratio
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    16.7%
    Lymphocyte count decreased
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    16.7%
    Prothrombin time prolonged
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    16.7%
    White blood cell count decreased
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    16.7%
    Alanine aminotransferase increased
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    11.1%
    0
    0%
    Amylase increased
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    11.1%
    1
    16.7%
    Aspartate aminotransferase increased
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    2
    22.2%
    0
    0%
    Blood alkaline phosphatase increased
    1
    25%
    0
    0%
    1
    33.3%
    0
    0%
    1
    11.1%
    0
    0%
    Blood creatinine increased
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    2
    22.2%
    1
    16.7%
    Blood phosphorus decreased
    1
    25%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Blood urea increased
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    11.1%
    0
    0%
    Gamma glutamyltransferase increased
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    11.1%
    0
    0%
    Lipase increased
    1
    25%
    0
    0%
    1
    33.3%
    0
    0%
    1
    11.1%
    0
    0%
    Hypercalcaemia
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    11.1%
    1
    16.7%
    Hyperglycaemia
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    11.1%
    0
    0%
    Hyperkalaemia
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    11.1%
    0
    0%
    Hypermagnesaemia
    0
    0%
    0
    0%
    1
    33.3%
    0
    0%
    0
    0%
    0
    0%
    Hyperuricaemia
    1
    25%
    0
    0%
    0
    0%
    0
    0%
    1
    11.1%
    0
    0%
    Hypoalbuminaemia
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    11.1%
    0
    0%
    Hypokalaemia
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    2
    22.2%
    0
    0%
    Hypomagnesaemia
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    2
    22.2%
    0
    0%
    Hyponatraemia
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    2
    22.2%
    1
    16.7%
    proteinuria
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    11.1%
    0
    0%
    3. Primary Outcome
    Title Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAES in Dose-escalation Phase
    Description Number of participants in dose-escalation phase with abnormal vital signs reported as TEAEs are reported. Abnormal vital signs is defined as any abnormal finding in the vital sign parameters (blood pressure, heart rate, body temperature, and respiratory rate). Abnormal physical examination findings are defined as any abnormal finding in the following body systems: head and neck, respiratory, cardiovascular, gastrointestinal, urogenital, musculoskeletal, neurological, psychiatric, dermatological, hematologic/lymphatic, and endocrine systems, and weight.
    Time Frame Day 1 through 90 days post end of treatment (approximately 5 years 10 months)

    Outcome Measure Data

    Analysis Population Description
    As-treated population included those participants who received any study drug (MEDI0680, durvalumab, or nivolumab) and grouped according to actual treatment received.
    Arm/Group Title MEDI0680 0.1 mg/kg + Durvalumab 3 mg MEDI0680 0.1 mg/kg + Durvalumab 10 mg MEDI0680 0.5 mg/kg + Durvalumab 10 mg MEDI0680 2.5 mg/kg + Durvalumab 10 mg MEDI0680 10 mg/kg + Durvalumab 10 mg MEDI0680 20 mg/kg + Durvalumab 10 mg
    Arm/Group Description Participants in dose-escalation phase received IV infusion of MEDI0680 0.1 mg/kg and durvalumab 3 mg/kg every 2 weeks (Q2W) for up to 12 months. Participants in dose-escalation phase received IV infusion of MEDI0680 0.1 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months. Participants in dose-escalation phase received IV infusion of MEDI0680 0.5 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months. Participants in dose-escalation phase received IV infusion of MEDI0680 2.5 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months. Participants in dose-escalation phase received IV infusion of MEDI0680 10 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months. Participants in dose-escalation phase received IV infusion of MEDI0680 20 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months.
    Measure Participants 4 5 3 3 9 6
    Atrial fibrillation
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    11.1%
    0
    0%
    Palpitations
    1
    25%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Sinus tachycardia
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    11.1%
    0
    0%
    Tachycardia
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    16.7%
    Pyrexia
    0
    0%
    0
    0%
    2
    66.7%
    0
    0%
    3
    33.3%
    1
    16.7%
    Weight decreased
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    11.1%
    1
    16.7%
    Hypertension
    1
    25%
    0
    0%
    0
    0%
    0
    0%
    1
    11.1%
    1
    16.7%
    4. Primary Outcome
    Title Number of Participants With Abnormal Electrocardiograms (ECGs) Reported as TEAEs in Dose-escalation Phase
    Description Number of participants in dose-escalation phase with abnormal ECG parameters reported as TEAEs are reported.
    Time Frame Day 1 through 90 days post end of treatment (approximately 5 years 10 months)

    Outcome Measure Data

    Analysis Population Description
    As-treated population included those participants who received any study drug (MEDI0680, durvalumab, or nivolumab) and grouped according to actual treatment received.
    Arm/Group Title MEDI0680 0.1 mg/kg + Durvalumab 3 mg MEDI0680 0.1 mg/kg + Durvalumab 10 mg MEDI0680 0.5 mg/kg + Durvalumab 10 mg MEDI0680 2.5 mg/kg + Durvalumab 10 mg MEDI0680 10 mg/kg + Durvalumab 10 mg MEDI0680 20 mg/kg + Durvalumab 10 mg
    Arm/Group Description Participants in dose-escalation phase received IV infusion of MEDI0680 0.1 mg/kg and durvalumab 3 mg/kg every 2 weeks (Q2W) for up to 12 months. Participants in dose-escalation phase received IV infusion of MEDI0680 0.1 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months. Participants in dose-escalation phase received IV infusion of MEDI0680 0.5 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months. Participants in dose-escalation phase received IV infusion of MEDI0680 2.5 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months. Participants in dose-escalation phase received IV infusion of MEDI0680 10 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months. Participants in dose-escalation phase received IV infusion of MEDI0680 20 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months.
    Measure Participants 4 5 3 3 9 6
    Palpitations
    1
    25%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Atrial fibrillation
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    11.1%
    0
    0%
    Sinus tachycardia
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    11.1%
    0
    0%
    Pericardial effusion
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    11.1%
    0
    0%
    Tachycardia
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    16.7%
    5. Primary Outcome
    Title Objective Response Rate (ORR) Based on Investigator-assessed Response Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) in Dose-expansion Phase
    Description The ORR is defined as best overall response of confirmed complete response (CR) or confirmed partial response (PR) based on RECIST v1.1. 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 non-target lesion. A confirmed CR or PR is defined as 2 CRs or 2 PRs that were separated by at least 4 weeks with no evidence of progression in-between.
    Time Frame From baseline (Day -42 to Day -1) through disease progression or end of treatment (approximately 5 years 10 months)

    Outcome Measure Data

    Analysis Population Description
    As-treated population included those participants who received any study drug (MEDI0680, durvalumab, or nivolumab) and grouped according to actual treatment received.
    Arm/Group Title MEDI0680 20 mg/kg MEDI0680 20 mg/kg + Durvalumab 750 mg Nivolumab 240 mg
    Arm/Group Description Participants in dose-expansion phase received IV infusion of MEDI0680 20 mg/kg Q2W until unacceptable toxicity, confirmed disease progression, development of other reason for treatment discontinuation, or for a maximum of 2 years, whichever occurred first. Participants in dose-expansion phase received IV infusion of MEDI0680 20 mg/kg and durvalumab 750 mg/kg Q2W until unacceptable toxicity, confirmed disease progression, development of other reason for treatment discontinuation, or for a maximum of 2 years, whichever occurred first. Participants in dose-expansion phase received IV infusion of nivolumab 240 mg Q2W until unacceptable toxicity, confirmed disease progression, development of other reason for treatment discontinuation, or for a maximum of 2 years, whichever occurred first.
    Measure Participants 4 42 21
    Number (95% Confidence Interval) [Percentage of participants]
    0
    0%
    16.7
    334%
    23.8
    793.3%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection MEDI0680 0.1 mg/kg + Durvalumab 3 mg, MEDI0680 0.5 mg/kg + Durvalumab 10 mg
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.5494
    Comments
    Method Fisher Exact
    Comments
    Method of Estimation Estimation Parameter Rate difference
    Estimated Value -23.8
    Confidence Interval (2-Sided) 95%
    -72.8 to 31.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection MEDI0680 0.1 mg/kg + Durvalumab 10 mg, MEDI0680 0.5 mg/kg + Durvalumab 10 mg
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.5130
    Comments
    Method Fisher Exact
    Comments
    Method of Estimation Estimation Parameter Rate difference
    Estimated Value -7.1
    Confidence Interval (2-Sided) 95%
    -33.6 to 20.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    6. Secondary Outcome
    Title Best Overall Response (BOR) Based on Investigator-assessed RECIST v1.1 in Dose-expansion Phase
    Description The BOR includes CR, PR, stable disease (SD), progressive disease (PD), and non-evaluable (NE) based on RECIST v1.1. 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% decrease 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 baseline (Day -42 to Day -1) through disease progression or end of treatment (approximately 5 years 10 months)

    Outcome Measure Data

    Analysis Population Description
    As-treated population included those participants who received any study drug (MEDI0680, durvalumab, or nivolumab) and grouped according to actual treatment received.
    Arm/Group Title MEDI0680 20 mg/kg MEDI0680 20 mg/kg + Durvalumab 750 mg Nivolumab 240 mg
    Arm/Group Description Participants in dose-expansion phase received IV infusion of MEDI0680 20 mg/kg Q2W until unacceptable toxicity, confirmed disease progression, development of other reason for treatment discontinuation, or for a maximum of 2 years, whichever occurred first. Participants in dose-expansion phase received IV infusion of MEDI0680 20 mg/kg and durvalumab 750 mg/kg Q2W until unacceptable toxicity, confirmed disease progression, development of other reason for treatment discontinuation, or for a maximum of 2 years, whichever occurred first. Participants in dose-expansion phase received IV infusion of nivolumab 240 mg Q2W until unacceptable toxicity, confirmed disease progression, development of other reason for treatment discontinuation, or for a maximum of 2 years, whichever occurred first.
    Measure Participants 4 42 21
    CR
    0
    0%
    2
    40%
    0
    0%
    PR
    0
    0%
    5
    100%
    5
    166.7%
    SD
    3
    75%
    17
    340%
    8
    266.7%
    PD
    1
    25%
    17
    340%
    6
    200%
    NE
    0
    0%
    1
    20%
    2
    66.7%
    7. Secondary Outcome
    Title Disease Control Rate (DCR) Based on Investigator-assessed RECIST v1.1 in Dose-expansion Phase
    Description 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 4 weeks 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) that were separated by at least 4 weeks 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. The DCR at >= 8 weeks and >=24 weeks are reported.
    Time Frame From baseline (Day -42 to Day -1) through disease progression or end of treatment (approximately 5 years 10 months)

    Outcome Measure Data

    Analysis Population Description
    As-treated population included those participants who received any study drug (MEDI0680, durvalumab, or nivolumab) and grouped according to actual treatment received.
    Arm/Group Title MEDI0680 20 mg/kg MEDI0680 20 mg/kg + Durvalumab 750 mg Nivolumab 240 mg
    Arm/Group Description Participants in dose-expansion phase received IV infusion of MEDI0680 20 mg/kg Q2W until unacceptable toxicity, confirmed disease progression, development of other reason for treatment discontinuation, or for a maximum of 2 years, whichever occurred first. Participants in dose-expansion phase received IV infusion of MEDI0680 20 mg/kg and durvalumab 750 mg/kg Q2W until unacceptable toxicity, confirmed disease progression, development of other reason for treatment discontinuation, or for a maximum of 2 years, whichever occurred first. Participants in dose-expansion phase received IV infusion of nivolumab 240 mg Q2W until unacceptable toxicity, confirmed disease progression, development of other reason for treatment discontinuation, or for a maximum of 2 years, whichever occurred first.
    Measure Participants 4 42 21
    DCR at >=8 weeks
    75.0
    1875%
    57.1
    1142%
    61.9
    2063.3%
    DCR at >=24 weeks
    50.0
    1250%
    38.1
    762%
    38.1
    1270%
    8. Secondary Outcome
    Title Time to Response (TTR) Based on Investigator-assessed RECIST v1.1 in Dose-expansion Phase
    Description The TTR is defined as the time from the first dose of treatment until the first documentation of a subsequently confirmed OR (confirmed CR or confirmed PR) 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 4 weeks 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) that were separated by at least 4 weeks with no evidence of progression in-between. The TTR was estimated using Kaplan-Meier method.
    Time Frame From baseline (Day -42 to Day -1) through disease progression or end of treatment (approximately 5 years 10 months)

    Outcome Measure Data

    Analysis Population Description
    As-treated population included those participants who received any study drug (MEDI0680, durvalumab, or nivolumab) and grouped according to actual treatment received. The TTR was analyzed for those participants who achieved OR.
    Arm/Group Title MEDI0680 20 mg/kg MEDI0680 20 mg/kg + Durvalumab 750 mg Nivolumab 240 mg
    Arm/Group Description Participants in dose-expansion phase received IV infusion of MEDI0680 20 mg/kg Q2W until unacceptable toxicity, confirmed disease progression, development of other reason for treatment discontinuation, or for a maximum of 2 years, whichever occurred first. Participants in dose-expansion phase received IV infusion of MEDI0680 20 mg/kg and durvalumab 750 mg/kg Q2W until unacceptable toxicity, confirmed disease progression, development of other reason for treatment discontinuation, or for a maximum of 2 years, whichever occurred first. Participants in dose-expansion phase received IV infusion of nivolumab 240 mg Q2W until unacceptable toxicity, confirmed disease progression, development of other reason for treatment discontinuation, or for a maximum of 2 years, whichever occurred first.
    Measure Participants 0 7 5
    Median (95% Confidence Interval) [Months]
    1.8
    1.8
    9. Secondary Outcome
    Title Duration of Response (DoR) Based on Investigator-assessed RECIST v1.1 in Dose-expansion Phase
    Description 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 4 weeks 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) that were separated by at least 4 weeks with no evidence of progression in-between. The PD is defined at least 20% decrease in the sum of diameters of target lesions (compared to baseline) and/or new lesion. The DoR was estimated using Kaplan-Meier method.
    Time Frame From baseline (Day -42 to Day -1) through disease progression or end of treatment (approximately 5 years 10 months)

    Outcome Measure Data

    Analysis Population Description
    As-treated population included those participants who received any study drug (MEDI0680, durvalumab, or nivolumab) and grouped according to actual treatment received. The DoR was analyzed for those participants who achieved OR.
    Arm/Group Title MEDI0680 20 mg/kg MEDI0680 20 mg/kg + Durvalumab 750 mg Nivolumab 240 mg
    Arm/Group Description Participants in dose-expansion phase received IV infusion of MEDI0680 20 mg/kg Q2W until unacceptable toxicity, confirmed disease progression, development of other reason for treatment discontinuation, or for a maximum of 2 years, whichever occurred first. Participants in dose-expansion phase received IV infusion of MEDI0680 20 mg/kg and durvalumab 750 mg/kg Q2W until unacceptable toxicity, confirmed disease progression, development of other reason for treatment discontinuation, or for a maximum of 2 years, whichever occurred first. Participants in dose-expansion phase received IV infusion of nivolumab 240 mg Q2W until unacceptable toxicity, confirmed disease progression, development of other reason for treatment discontinuation, or for a maximum of 2 years, whichever occurred first.
    Measure Participants 0 7 5
    Median (95% Confidence Interval) [Months]
    NA
    NA
    10. Secondary Outcome
    Title Progression Free Survival (PFS) Based on Investigator-assessed RECIST v1.1 in Dose-expansion Phase
    Description 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 PFS was estimated using Kaplan-Meier method.
    Time Frame From baseline (Day -42 to Day -1) through disease progression or end of treatment (approximately 5 years 10 months)

    Outcome Measure Data

    Analysis Population Description
    As-treated population included those participants who received any study drug (MEDI0680, durvalumab, or nivolumab) and grouped according to actual treatment received.
    Arm/Group Title MEDI0680 20 mg/kg MEDI0680 20 mg/kg + Durvalumab 750 mg Nivolumab 240 mg
    Arm/Group Description Participants in dose-expansion phase received IV infusion of MEDI0680 20 mg/kg Q2W until unacceptable toxicity, confirmed disease progression, development of other reason for treatment discontinuation, or for a maximum of 2 years, whichever occurred first. Participants in dose-expansion phase received IV infusion of MEDI0680 20 mg/kg and durvalumab 750 mg/kg Q2W until unacceptable toxicity, confirmed disease progression, development of other reason for treatment discontinuation, or for a maximum of 2 years, whichever occurred first. Participants in dose-expansion phase received IV infusion of nivolumab 240 mg Q2W until unacceptable toxicity, confirmed disease progression, development of other reason for treatment discontinuation, or for a maximum of 2 years, whichever occurred first.
    Measure Participants 4 42 21
    Median (95% Confidence Interval) [Months]
    5.5
    3.6
    3.6
    11. Secondary Outcome
    Title Overall Survival in Dose-expansion Phase
    Description 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 baseline (Day -42 to Day -1) through disease progression or end of treatment (approximately 5 years 10 months)

    Outcome Measure Data

    Analysis Population Description
    As-treated population included those participants who received any study drug (MEDI0680, durvalumab, or nivolumab) and grouped according to actual treatment received.
    Arm/Group Title MEDI0680 20 mg/kg MEDI0680 20 mg/kg + Durvalumab 750 mg Nivolumab 240 mg
    Arm/Group Description Participants in dose-expansion phase received IV infusion of MEDI0680 20 mg/kg Q2W until unacceptable toxicity, confirmed disease progression, development of other reason for treatment discontinuation, or for a maximum of 2 years, whichever occurred first. Participants in dose-expansion phase received IV infusion of MEDI0680 20 mg/kg and durvalumab 750 mg/kg Q2W until unacceptable toxicity, confirmed disease progression, development of other reason for treatment discontinuation, or for a maximum of 2 years, whichever occurred first. Participants in dose-expansion phase received IV infusion of nivolumab 240 mg Q2W until unacceptable toxicity, confirmed disease progression, development of other reason for treatment discontinuation, or for a maximum of 2 years, whichever occurred first.
    Measure Participants 4 42 21
    Median (95% Confidence Interval) [Months]
    19.9
    NA
    NA
    12. Secondary Outcome
    Title BOR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase
    Description The BOR includes CR, PR, SD, PD, and NE per Modified RECIST v1.1. 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% decrease 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 baseline (Day -42 to Day -1) through disease progression or EOT (approximately 12 months for each participant)

    Outcome Measure Data

    Analysis Population Description
    As-treated population included those participants who received any study drug (MEDI0680, durvalumab, or nivolumab) and grouped according to actual treatment received.
    Arm/Group Title MEDI0680 0.1 mg/kg + Durvalumab 3 mg MEDI0680 0.1 mg/kg + Durvalumab 10 mg MEDI0680 0.5 mg/kg + Durvalumab 10 mg MEDI0680 2.5 mg/kg + Durvalumab 10 mg MEDI0680 10 mg/kg + Durvalumab 10 mg MEDI0680 20 mg/kg + Durvalumab 10 mg
    Arm/Group Description Participants in dose-escalation phase received IV infusion of MEDI0680 0.1 mg/kg and durvalumab 3 mg/kg every 2 weeks (Q2W) for up to 12 months. Participants in dose-escalation phase received IV infusion of MEDI0680 0.1 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months. Participants in dose-escalation phase received IV infusion of MEDI0680 0.5 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months. Participants in dose-escalation phase received IV infusion of MEDI0680 2.5 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months. Participants in dose-escalation phase received IV infusion of MEDI0680 10 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months. Participants in dose-escalation phase received IV infusion of MEDI0680 20 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months.
    Measure Participants 4 5 3 3 9 6
    CR
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    11.1%
    0
    0%
    PR
    2
    50%
    0
    0%
    1
    33.3%
    0
    0%
    3
    33.3%
    4
    66.7%
    SD
    1
    25%
    1
    20%
    0
    0%
    1
    33.3%
    2
    22.2%
    1
    16.7%
    PD
    1
    25%
    3
    60%
    2
    66.7%
    1
    33.3%
    2
    22.2%
    1
    16.7%
    NE
    0
    0%
    1
    20%
    0
    0%
    1
    33.3%
    1
    11.1%
    0
    0%
    13. Secondary Outcome
    Title ORR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase
    Description The ORR is defined as best overall response of confirmed CR or confirmed PR based on modified RECIST v1.1. 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 non-target lesion. A confirmed CR or PR is defined as 2 CRs or 2 PRs that were separated by at least 4 weeks with no evidence of progression in-between.
    Time Frame From baseline (Day -42 to Day -1) through disease progression or EOT (approximately 12 months for each participant)

    Outcome Measure Data

    Analysis Population Description
    As-treated population included those participants who received any study drug (MEDI0680, durvalumab, or nivolumab) and grouped according to actual treatment received.
    Arm/Group Title MEDI0680 0.1 mg/kg + Durvalumab 3 mg MEDI0680 0.1 mg/kg + Durvalumab 10 mg MEDI0680 0.5 mg/kg + Durvalumab 10 mg MEDI0680 2.5 mg/kg + Durvalumab 10 mg MEDI0680 10 mg/kg + Durvalumab 10 mg MEDI0680 20 mg/kg + Durvalumab 10 mg
    Arm/Group Description Participants in dose-escalation phase received IV infusion of MEDI0680 0.1 mg/kg and durvalumab 3 mg/kg every 2 weeks (Q2W) for up to 12 months. Participants in dose-escalation phase received IV infusion of MEDI0680 0.1 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months. Participants in dose-escalation phase received IV infusion of MEDI0680 0.5 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months. Participants in dose-escalation phase received IV infusion of MEDI0680 2.5 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months. Participants in dose-escalation phase received IV infusion of MEDI0680 10 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months. Participants in dose-escalation phase received IV infusion of MEDI0680 20 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months.
    Measure Participants 4 5 3 3 9 6
    Number (95% Confidence Interval) [Percentage of participants]
    50.0
    1250%
    0
    0%
    33.3
    1110%
    0
    0%
    44.4
    493.3%
    66.7
    1111.7%
    14. Secondary Outcome
    Title DCR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase
    Description The DCR is defined as a BOR of confirmed CR, confirmed PR, or SD based on modified 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 4 weeks 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) that were separated by at least 4 weeks 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. The DCR at >= 8 weeks and >=24 weeks are reported.
    Time Frame From baseline (Day -42 to Day -1) through disease progression or EOT (approximately 12 months for each participant)

    Outcome Measure Data

    Analysis Population Description
    As-treated population included those participants who received any study drug (MEDI0680, durvalumab, or nivolumab) and grouped according to actual treatment received.
    Arm/Group Title MEDI0680 0.1 mg/kg + Durvalumab 3 mg MEDI0680 0.1 mg/kg + Durvalumab 10 mg MEDI0680 0.5 mg/kg + Durvalumab 10 mg MEDI0680 2.5 mg/kg + Durvalumab 10 mg MEDI0680 10 mg/kg + Durvalumab 10 mg MEDI0680 20 mg/kg + Durvalumab 10 mg
    Arm/Group Description Participants in dose-escalation phase received IV infusion of MEDI0680 0.1 mg/kg and durvalumab 3 mg/kg every 2 weeks (Q2W) for up to 12 months. Participants in dose-escalation phase received IV infusion of MEDI0680 0.1 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months. Participants in dose-escalation phase received IV infusion of MEDI0680 0.5 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months. Participants in dose-escalation phase received IV infusion of MEDI0680 2.5 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months. Participants in dose-escalation phase received IV infusion of MEDI0680 10 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months. Participants in dose-escalation phase received IV infusion of MEDI0680 20 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months.
    Measure Participants 4 5 3 3 9 6
    DCR at >= 8 weeks
    75.0
    1875%
    20.0
    400%
    33.3
    1110%
    33.3
    1110%
    66.7
    741.1%
    83.3
    1388.3%
    DCR at >= 24 weeks
    50.0
    1250%
    0
    0%
    33.3
    1110%
    0
    0%
    44.4
    493.3%
    83.3
    1388.3%
    15. Secondary Outcome
    Title TTR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase
    Description The TTR is defined as the time from the first dose of treatment until the first documentation of a subsequently confirmed OR (confirmed CR or confirmed PR) based on modified 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 4 weeks 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) that were separated by at least 4 weeks with no evidence of progression in-between. The TTR was estimated using Kaplan-Meier method.
    Time Frame From baseline (Day -42 to Day -1) through disease progression or EOT (approximately 12 months for each participant)

    Outcome Measure Data

    Analysis Population Description
    As-treated population included those participants who received any study drug (MEDI0680, durvalumab, or nivolumab) and grouped according to actual treatment received. The TTR was analyzed for those participants who achieved OR.
    Arm/Group Title MEDI0680 0.1 mg/kg + Durvalumab 3 mg MEDI0680 0.1 mg/kg + Durvalumab 10 mg MEDI0680 0.5 mg/kg + Durvalumab 10 mg MEDI0680 2.5 mg/kg + Durvalumab 10 mg MEDI0680 10 mg/kg + Durvalumab 10 mg MEDI0680 20 mg/kg + Durvalumab 10 mg
    Arm/Group Description Participants in dose-escalation phase received IV infusion of MEDI0680 0.1 mg/kg and durvalumab 3 mg/kg every 2 weeks (Q2W) for up to 12 months. Participants in dose-escalation phase received IV infusion of MEDI0680 0.1 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months. Participants in dose-escalation phase received IV infusion of MEDI0680 0.5 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months. Participants in dose-escalation phase received IV infusion of MEDI0680 2.5 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months. Participants in dose-escalation phase received IV infusion of MEDI0680 10 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months. Participants in dose-escalation phase received IV infusion of MEDI0680 20 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months.
    Measure Participants 2 0 1 0 4 4
    Median (95% Confidence Interval) [Months]
    2.6
    3.4
    3.5
    3.2
    16. Secondary Outcome
    Title DoR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase
    Description 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 modified 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 4 weeks 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) that were separated by at least 4 weeks with no evidence of progression in-between. The PD is defined at least 20% decrease in the sum of diameters of target lesions (compared to baseline) and/or new lesion. The DoR was estimated using Kaplan-Meier method.
    Time Frame From baseline (Day -42 to Day -1) through disease progression or EOT (approximately 12 months for each participant)

    Outcome Measure Data

    Analysis Population Description
    AAs-treated population included those participants who received any study drug (MEDI0680, durvalumab, or nivolumab) and grouped according to actual treatment received. The DoR was analyzed for those participants who achieved OR.
    Arm/Group Title MEDI0680 0.1 mg/kg + Durvalumab 3 mg MEDI0680 0.1 mg/kg + Durvalumab 10 mg MEDI0680 0.5 mg/kg + Durvalumab 10 mg MEDI0680 2.5 mg/kg + Durvalumab 10 mg MEDI0680 10 mg/kg + Durvalumab 10 mg MEDI0680 20 mg/kg + Durvalumab 10 mg
    Arm/Group Description Participants in dose-escalation phase received IV infusion of MEDI0680 0.1 mg/kg and durvalumab 3 mg/kg every 2 weeks (Q2W) for up to 12 months. Participants in dose-escalation phase received IV infusion of MEDI0680 0.1 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months. Participants in dose-escalation phase received IV infusion of MEDI0680 0.5 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months. Participants in dose-escalation phase received IV infusion of MEDI0680 2.5 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months. Participants in dose-escalation phase received IV infusion of MEDI0680 10 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months. Participants in dose-escalation phase received IV infusion of MEDI0680 20 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months.
    Measure Participants 2 0 1 0 4 4
    Median (95% Confidence Interval) [Months]
    16.8
    NA
    7.4
    NA
    17. Secondary Outcome
    Title PFS Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase
    Description The PFS is defined as the time from the start of study treatment until the first documentation of disease progression based on modified RECIST v1.1 or death due to any cause, whichever occurred first. The PFS was estimated using Kaplan-Meier method.
    Time Frame From baseline (Day -42 to Day -1) through disease progression or EOT (approximately 12 months for each participant)

    Outcome Measure Data

    Analysis Population Description
    As-treated population included those participants who received any study drug (MEDI0680, durvalumab, or nivolumab) and grouped according to actual treatment received.
    Arm/Group Title MEDI0680 0.1 mg/kg + Durvalumab 3 mg MEDI0680 0.1 mg/kg + Durvalumab 10 mg MEDI0680 0.5 mg/kg + Durvalumab 10 mg MEDI0680 2.5 mg/kg + Durvalumab 10 mg MEDI0680 10 mg/kg + Durvalumab 10 mg MEDI0680 20 mg/kg + Durvalumab 10 mg
    Arm/Group Description Participants in dose-escalation phase received IV infusion of MEDI0680 0.1 mg/kg and durvalumab 3 mg/kg every 2 weeks (Q2W) for up to 12 months. Participants in dose-escalation phase received IV infusion of MEDI0680 0.1 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months. Participants in dose-escalation phase received IV infusion of MEDI0680 0.5 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months. Participants in dose-escalation phase received IV infusion of MEDI0680 2.5 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months. Participants in dose-escalation phase received IV infusion of MEDI0680 10 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months. Participants in dose-escalation phase received IV infusion of MEDI0680 20 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months.
    Measure Participants 4 5 3 3 9 6
    Median (95% Confidence Interval) [Months]
    20.2
    1.7
    1.6
    1.8
    7.0
    23.4
    18. Secondary Outcome
    Title OS in Dose-escalation Phase
    Description 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 baseline (Day -42 to Day -1) through disease progression or EOT (approximately 12 months for each participant)

    Outcome Measure Data

    Analysis Population Description
    As-treated population included those participants who received any study drug (MEDI0680, durvalumab, or nivolumab) and grouped according to actual treatment received.
    Arm/Group Title MEDI0680 0.1 mg/kg + Durvalumab 3 mg MEDI0680 0.1 mg/kg + Durvalumab 10 mg MEDI0680 0.5 mg/kg + Durvalumab 10 mg MEDI0680 2.5 mg/kg + Durvalumab 10 mg MEDI0680 10 mg/kg + Durvalumab 10 mg MEDI0680 20 mg/kg + Durvalumab 10 mg
    Arm/Group Description Participants in dose-escalation phase received IV infusion of MEDI0680 0.1 mg/kg and durvalumab 3 mg/kg every 2 weeks (Q2W) for up to 12 months. Participants in dose-escalation phase received IV infusion of MEDI0680 0.1 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months. Participants in dose-escalation phase received IV infusion of MEDI0680 0.5 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months. Participants in dose-escalation phase received IV infusion of MEDI0680 2.5 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months. Participants in dose-escalation phase received IV infusion of MEDI0680 10 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months. Participants in dose-escalation phase received IV infusion of MEDI0680 20 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months.
    Measure Participants 4 5 3 3 9 6
    Median (95% Confidence Interval) [Months]
    16.3
    NA
    14.7
    7.9
    12.8
    NA
    19. Secondary Outcome
    Title Number of Participants With TEAEs and TESAEs in Dose-expansion Phase
    Description An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An 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 Day 1 through 90 days post end of treatment (approximately 5 years 10 months)

    Outcome Measure Data

    Analysis Population Description
    As-treated population included those participants who received any study drug (MEDI0680, durvalumab, or nivolumab) and grouped according to actual treatment received.
    Arm/Group Title MEDI0680 20 mg/kg MEDI0680 20 mg/kg + Durvalumab 750 mg Nivolumab 240 mg
    Arm/Group Description Participants in dose-expansion phase received IV infusion of MEDI0680 20 mg/kg Q2W until unacceptable toxicity, confirmed disease progression, development of other reason for treatment discontinuation, or for a maximum of 2 years, whichever occurred first. Participants in dose-expansion phase received IV infusion of MEDI0680 20 mg/kg and durvalumab 750 mg/kg Q2W until unacceptable toxicity, confirmed disease progression, development of other reason for treatment discontinuation, or for a maximum of 2 years, whichever occurred first. Participants in dose-expansion phase received IV infusion of nivolumab 240 mg Q2W until unacceptable toxicity, confirmed disease progression, development of other reason for treatment discontinuation, or for a maximum of 2 years, whichever occurred first.
    Measure Participants 4 42 21
    Any TEAE
    4
    100%
    42
    840%
    20
    666.7%
    Any TESAE
    3
    75%
    22
    440%
    13
    433.3%
    20. Secondary Outcome
    Title Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase
    Description Number of participants in dose-expansion phase with abnormal clinical laboratory parameters reported as TEAEs are reported. Abnormal clinical laboratory parameters defined as any abnormal finding during analysis of serum chemistry, hematology, coagulation, and urine.
    Time Frame Day 1 through 90 days post end of treatment (approximately 5 years 10 months)

    Outcome Measure Data

    Analysis Population Description
    As-treated population included those participants who received any study drug (MEDI0680, durvalumab, or nivolumab) and grouped according to actual treatment received.
    Arm/Group Title MEDI0680 20 mg/kg MEDI0680 20 mg/kg + Durvalumab 750 mg Nivolumab 240 mg
    Arm/Group Description Participants in dose-expansion phase received IV infusion of MEDI0680 20 mg/kg Q2W until unacceptable toxicity, confirmed disease progression, development of other reason for treatment discontinuation, or for a maximum of 2 years, whichever occurred first. Participants in dose-expansion phase received IV infusion of MEDI0680 20 mg/kg and durvalumab 750 mg/kg Q2W until unacceptable toxicity, confirmed disease progression, development of other reason for treatment discontinuation, or for a maximum of 2 years, whichever occurred first. Participants in dose-expansion phase received IV infusion of nivolumab 240 mg Q2W until unacceptable toxicity, confirmed disease progression, development of other reason for treatment discontinuation, or for a maximum of 2 years, whichever occurred first.
    Measure Participants 4 42 21
    Anaemia
    1
    25%
    6
    120%
    5
    166.7%
    Neutropenia
    0
    0%
    1
    20%
    0
    0%
    Blood iron decreased
    0
    0%
    0
    0%
    1
    33.3%
    Lymphocyte count decreased
    0
    0%
    0
    0%
    1
    33.3%
    Neutrophil count decreased
    1
    25%
    1
    20%
    0
    0%
    Platelet count decreased
    0
    0%
    0
    0%
    1
    33.3%
    Platelet count increased
    0
    0%
    0
    0%
    1
    33.3%
    Prothrombin time prolonged
    0
    0%
    0
    0%
    1
    33.3%
    White blood cell count increased
    0
    0%
    0
    0%
    1
    33.3%
    Alanine aminotransferase increased
    1
    25%
    1
    20%
    3
    100%
    Amylase decreased
    0
    0%
    0
    0%
    1
    33.3%
    Amylase increased
    1
    25%
    3
    60%
    3
    100%
    Aspartate aminotransferase increased
    1
    25%
    2
    40%
    3
    100%
    Blood alkaline phosphatase increased
    0
    0%
    0
    0%
    1
    33.3%
    Blood bilirubin increased
    0
    0%
    0
    0%
    1
    33.3%
    Blood creatine increased
    1
    25%
    1
    20%
    0
    0%
    Blood creatine phosphokinase increased
    0
    0%
    1
    20%
    0
    0%
    Blood creatinine increased
    1
    25%
    4
    80%
    3
    100%
    Blood glucose increased
    0
    0%
    0
    0%
    1
    33.3%
    Blood triglycerides increased
    0
    0%
    1
    20%
    1
    33.3%
    C-reactive protein increased
    0
    0%
    1
    20%
    1
    33.3%
    Lipase increased
    1
    25%
    4
    80%
    2
    66.7%
    Transaminases increased
    0
    0%
    1
    20%
    0
    0%
    Hypercalcaemia
    0
    0%
    6
    120%
    2
    66.7%
    Hyperglycaemia
    0
    0%
    1
    20%
    0
    0%
    Hyperkalaemia
    0
    0%
    2
    40%
    2
    66.7%
    Hypertriglyceridaemia
    0
    0%
    1
    20%
    0
    0%
    Hypoalbuminaemia
    0
    0%
    2
    40%
    0
    0%
    Hypocalcaemia
    0
    0%
    1
    20%
    0
    0%
    Hypoglycaemia
    0
    0%
    1
    20%
    0
    0%
    Hypokalaemia
    0
    0%
    5
    100%
    2
    66.7%
    Hypomagnesaemia
    0
    0%
    4
    80%
    2
    66.7%
    Hyponatraemia
    1
    25%
    3
    60%
    1
    33.3%
    Hypophosphataemia
    0
    0%
    1
    20%
    3
    100%
    Urine abnormality
    0
    0%
    1
    20%
    0
    0%
    Blood thyroid stimulating hormone increased
    0
    0%
    2
    40%
    2
    66.7%
    Blood urine present
    0
    0%
    0
    0%
    1
    33.3%
    21. Secondary Outcome
    Title Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Dose-expansion Phase
    Description Number of participants in dose-expansion phase with abnormal vital signs reported as TEAEs are reported. Abnormal vital signs is defined as any abnormal finding in the vital sign parameters (blood pressure, heart rate, body temperature, and respiratory rate). Abnormal physical examination findings are defined as any abnormal finding in the following body systems: head and neck, respiratory, cardiovascular, gastrointestinal, urogenital, musculoskeletal, neurological, psychiatric, dermatological, hematologic/lymphatic, and endocrine systems, and weight.
    Time Frame Day 1 through 90 days post end of treatment (approximately 5 years 10 months)

    Outcome Measure Data

    Analysis Population Description
    As-treated population included those participants who received any study drug (MEDI0680, durvalumab, or nivolumab) and grouped according to actual treatment received.
    Arm/Group Title MEDI0680 20 mg/kg MEDI0680 20 mg/kg + Durvalumab 750 mg Nivolumab 240 mg
    Arm/Group Description Participants in dose-expansion phase received IV infusion of MEDI0680 20 mg/kg Q2W until unacceptable toxicity, confirmed disease progression, development of other reason for treatment discontinuation, or for a maximum of 2 years, whichever occurred first. Participants in dose-expansion phase received IV infusion of MEDI0680 20 mg/kg and durvalumab 750 mg/kg Q2W until unacceptable toxicity, confirmed disease progression, development of other reason for treatment discontinuation, or for a maximum of 2 years, whichever occurred first. Participants in dose-expansion phase received IV infusion of nivolumab 240 mg Q2W until unacceptable toxicity, confirmed disease progression, development of other reason for treatment discontinuation, or for a maximum of 2 years, whichever occurred first.
    Measure Participants 4 42 21
    Atrial fibrillation
    0
    0%
    2
    40%
    1
    33.3%
    Tachycardia
    0
    0%
    1
    20%
    0
    0%
    Pyrexia
    2
    50%
    9
    180%
    2
    66.7%
    Weight decreased
    0
    0%
    5
    100%
    0
    0%
    Weight increased
    0
    0%
    3
    60%
    0
    0%
    Hypoxia
    0
    0%
    1
    20%
    1
    33.3%
    Hypertension
    1
    25%
    5
    100%
    0
    0%
    Hypotension
    1
    25%
    2
    40%
    1
    33.3%
    22. Secondary Outcome
    Title Number of Participants With Abnormal ECGs Reported as TEAEs in Dose-expansion Phase
    Description Number of participants in dose-expansion phase with abnormal ECG parameters reported as TEAEs are reported.
    Time Frame Day 1 through 90 days post end of treatment (approximately 5 years 10 months)

    Outcome Measure Data

    Analysis Population Description
    As-treated population included those participants who received any study drug (MEDI0680, durvalumab, or nivolumab) and grouped according to actual treatment received.
    Arm/Group Title MEDI0680 20 mg/kg MEDI0680 20 mg/kg + Durvalumab 750 mg Nivolumab 240 mg
    Arm/Group Description Participants in dose-expansion phase received IV infusion of MEDI0680 20 mg/kg Q2W until unacceptable toxicity, confirmed disease progression, development of other reason for treatment discontinuation, or for a maximum of 2 years, whichever occurred first. Participants in dose-expansion phase received IV infusion of MEDI0680 20 mg/kg and durvalumab 750 mg/kg Q2W until unacceptable toxicity, confirmed disease progression, development of other reason for treatment discontinuation, or for a maximum of 2 years, whichever occurred first. Participants in dose-expansion phase received IV infusion of nivolumab 240 mg Q2W until unacceptable toxicity, confirmed disease progression, development of other reason for treatment discontinuation, or for a maximum of 2 years, whichever occurred first.
    Measure Participants 4 42 21
    Angina pectoris
    1
    25%
    1
    20%
    0
    0%
    Tachycardia
    0
    0%
    1
    20%
    0
    0%
    Atrial fibrillation
    0
    0%
    2
    40%
    1
    33.3%
    Cardiac failure congestive
    0
    0%
    0
    0%
    1
    33.3%
    23. Secondary Outcome
    Title Antitumor Activity of MEDI0680 and Durvalumab Versus Nivolumab Monotherapy in Immunotherapy-Naïve Participants With Advanced or Metastatic Clear-cell Renal Cell Carcinoma (ccRCC) Based on Blinded Independent Central Review (BICR) in Dose-expansion Phase
    Description
    Time Frame From baseline (Day -42 to Day -1) through disease progression or end of treatment (approximately 5 years 10 months)

    Outcome Measure Data

    Analysis Population Description
    The study did not meet its primary endpoint of demonstrating superior antitumor effect of MEDI0680 in combination with durvalumab versus nivolumab monotherapy in immunotherapy-naïve participants with advanced or metastatic ccRCC as assessed by the investigator using RECIST v1.1. Therefore, the decision was made not to perform the BICR analysis for antitumor activity and hence data were not collected.
    Arm/Group Title MEDI0680 20 mg/kg MEDI0680 20 mg/kg + Durvalumab 750 mg Nivolumab 240 mg
    Arm/Group Description Participants in dose-expansion phase received IV infusion of MEDI0680 20 mg/kg Q2W until unacceptable toxicity, confirmed disease progression, development of other reason for treatment discontinuation, or for a maximum of 2 years, whichever occurred first. Participants in dose-expansion phase received IV infusion of MEDI0680 20 mg/kg and durvalumab 750 mg/kg Q2W until unacceptable toxicity, confirmed disease progression, development of other reason for treatment discontinuation, or for a maximum of 2 years, whichever occurred first. Participants in dose-expansion phase received IV infusion of nivolumab 240 mg Q2W until unacceptable toxicity, confirmed disease progression, development of other reason for treatment discontinuation, or for a maximum of 2 years, whichever occurred first.
    Measure Participants 0 0 0
    24. Secondary Outcome
    Title Percent Change From Baseline in Tumor Size in Dose-escalation Phase (Based on Investigator-assessed Modified RECIST v1.1) and Dose-expansion Phase (Based on Investigator-assessed RECIST v1.1)
    Description
    Time Frame From baseline (Day -42 to Day -1) through disease progression or EOT (approximately 12 months for each participant for dose-escalation phase and approximately 5 years 10 months for dose-expansion phase)

    Outcome Measure Data

    Analysis Population Description
    Per the Statistical Analysis Plan, the data for percent change from baseline in target lesion was to be presented using Spider plot analysis. Hence, numeric data were not collected for this outcome measure.
    Arm/Group Title MEDI0680 0.1 mg/kg + Durvalumab 3 mg MEDI0680 0.1 mg/kg + Durvalumab 10 mg MEDI0680 0.5 mg/kg + Durvalumab 10 mg MEDI0680 2.5 mg/kg + Durvalumab 10 mg MEDI0680 10 mg/kg + Durvalumab 10 mg MEDI0680 20 mg/kg + Durvalumab 10 mg MEDI0680 20 mg/kg MEDI0680 20 mg/kg + Durvalumab 750 mg Nivolumab 240 mg
    Arm/Group Description Participants in dose-escalation phase received IV infusion of MEDI0680 0.1 mg/kg and durvalumab 3 mg/kg every 2 weeks (Q2W) for up to 12 months. Participants in dose-escalation phase received IV infusion of MEDI0680 0.1 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months. Participants in dose-escalation phase received IV infusion of MEDI0680 0.5 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months. Participants in dose-escalation phase received IV infusion of MEDI0680 2.5 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months. Participants in dose-escalation phase received IV infusion of MEDI0680 10 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months. Participants in dose-escalation phase received IV infusion of MEDI0680 20 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months. Participants in dose-expansion phase received IV infusion of MEDI0680 20 mg/kg Q2W until unacceptable toxicity, confirmed disease progression, development of other reason for treatment discontinuation, or for a maximum of 2 years, whichever occurred first. Participants in dose-expansion phase received IV infusion of MEDI0680 20 mg/kg and durvalumab 750 mg/kg Q2W until unacceptable toxicity, confirmed disease progression, development of other reason for treatment discontinuation, or for a maximum of 2 years, whichever occurred first. Participants in dose-expansion phase received IV infusion of nivolumab 240 mg Q2W until unacceptable toxicity, confirmed disease progression, development of other reason for treatment discontinuation, or for a maximum of 2 years, whichever occurred first.
    Measure Participants 0 0 0 0 0 0 0 0 0
    25. Secondary Outcome
    Title Serum Concentration of MEDI0680 in Dose-escalation and Dose-expansion Phases
    Description Serum concentration of MEDI0680 were assessed using parameters Cmin (pre-dose) and Cmax (end of infusion), where Cmin was trough concentration and Cmax was peak concentration.
    Time Frame Pre-dose and end of infusion on Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1

    Outcome Measure Data

    Analysis Population Description
    As-treated population included those participants who received MEDI0680 and grouped according to actual treatment received. The "Number of participants Analyzed" denotes the number of participants who had quantifiable and calculable serum samples at the specified time points.
    Arm/Group Title MEDI0680 0.1 mg/kg + Durvalumab 3 mg MEDI0680 0.1 mg/kg + Durvalumab 10 mg MEDI0680 0.5 mg/kg + Durvalumab 10 mg MEDI0680 2.5 mg/kg + Durvalumab 10 mg MEDI0680 10 mg/kg + Durvalumab 10 mg MEDI0680 20 mg/kg + Durvalumab 10 mg MEDI0680 20 mg/kg MEDI0680 20 mg/kg + Durvalumab 750 mg
    Arm/Group Description Participants in dose-escalation phase received IV infusion of MEDI0680 0.1 mg/kg and durvalumab 3 mg/kg every 2 weeks (Q2W) for up to 12 months. Participants in dose-escalation phase received IV infusion of MEDI0680 0.1 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months. Participants in dose-escalation phase received IV infusion of MEDI0680 0.5 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months. Participants in dose-escalation phase received IV infusion of MEDI0680 2.5 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months. Participants in dose-escalation phase received IV infusion of MEDI0680 10 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months. Participants in dose-escalation phase received IV infusion of MEDI0680 20 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months. Participants in dose-expansion phase received IV infusion of MEDI0680 20 mg/kg Q2W until unacceptable toxicity, confirmed disease progression, development of other reason for treatment discontinuation, or for a maximum of 2 years, whichever occurred first. Participants in dose-expansion phase received IV infusion of MEDI0680 20 mg/kg and durvalumab 750 mg/kg Q2W until unacceptable toxicity, confirmed disease progression, development of other reason for treatment discontinuation, or for a maximum of 2 years, whichever occurred first.
    Measure Participants 4 5 3 3 9 6 4 40
    Cmin at Cycle1 Day1
    NA
    (NA)
    NA
    (NA)
    NA
    (NA)
    NA
    (NA)
    NA
    (NA)
    NA
    (NA)
    NA
    (NA)
    NA
    (NA)
    Cmax at Cycle1 Day1
    4.330
    (26.18)
    3.877
    (54.68)
    16.36
    (26.46)
    69.28
    (24.76)
    272.4
    (24.62)
    529.9
    (29.84)
    668.8
    (21.04)
    135.9
    (4007)
    Cmin at Cycle1 Day15
    1.143
    (22.70)
    0.9937
    (35.93)
    4.428
    (62.38)
    18.67
    (12.88)
    46.87
    (559.4)
    205.8
    (24.56)
    Cmax at Cycle1 Day15
    5.420
    (21.61)
    3.835
    (25.30)
    20.52
    (26.26)
    87.78
    (20.69)
    348.1
    (27.78)
    716.8
    (26.72)
    Cmin at Cycle2 Day1
    1.645
    (49.08)
    1.361
    (38.07)
    7.879
    (52.74)
    31.81
    (4.480)
    155.7
    (24.20)
    378.0
    (17.95)
    308.6
    (30.45)
    253.9
    (52.11)
    Cmax at Cycle2 Day1
    3.515
    (145.9)
    3.688
    (80.17)
    17.28
    (56.32)
    92.07
    (17.72)
    440.7
    (28.18)
    860.8
    (13.82)
    936.1
    (24.91)
    586.6
    (63.42)
    26. Secondary Outcome
    Title Serum Concentration of Durvalumab in Dose-escalation and Dose-expansion Phases
    Description Serum concentration of durvalumab were assessed using parameters Cmin (pre-dose) and Cmax (end of infusion), where Cmin was trough concentration and Cmax was peak concentration.
    Time Frame Pre-dose and end of infusion on Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1

    Outcome Measure Data

    Analysis Population Description
    As-treated population included those participants who received durvalumab and grouped according to actual treatment received. The "Number of participants Analyzed" denotes the number of participants who had quantifiable and calculable serum samples at the specified time points.
    Arm/Group Title MEDI0680 0.1 mg/kg + Durvalumab 3 mg MEDI0680 0.1 mg/kg + Durvalumab 10 mg MEDI0680 0.5 mg/kg + Durvalumab 10 mg MEDI0680 2.5 mg/kg + Durvalumab 10 mg MEDI0680 10 mg/kg + Durvalumab 10 mg MEDI0680 20 mg/kg + Durvalumab 10 mg MEDI0680 20 mg/kg + Durvalumab 750 mg
    Arm/Group Description Participants in dose-escalation phase received IV infusion of MEDI0680 0.1 mg/kg and durvalumab 3 mg/kg every 2 weeks (Q2W) for up to 12 months. Participants in dose-escalation phase received IV infusion of MEDI0680 0.1 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months. Participants in dose-escalation phase received IV infusion of MEDI0680 0.5 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months. Participants in dose-escalation phase received IV infusion of MEDI0680 2.5 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months. Participants in dose-escalation phase received IV infusion of MEDI0680 10 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months. Participants in dose-escalation phase received IV infusion of MEDI0680 20 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months. Participants in dose-expansion phase received IV infusion of MEDI0680 20 mg/kg and durvalumab 750 mg/kg Q2W until unacceptable toxicity, confirmed disease progression, development of other reason for treatment discontinuation, or for a maximum of 2 years, whichever occurred first.
    Measure Participants 4 5 3 3 9 6 41
    Cmin at Cycle1 Day1
    NA
    (NA)
    NA
    (NA)
    NA
    (NA)
    NA
    (NA)
    NA
    (NA)
    NA
    (NA)
    NA
    (NA)
    Cmax at Cycle1 Day1
    65.47
    (10.02)
    216.1
    (25.14)
    213.8
    (9.943)
    188.0
    (17.82)
    248.0
    (27.20)
    253.9
    (11.35)
    186.9
    (33.42)
    Cmin at Cycle1 Day15
    19.62
    (16.49)
    63.02
    (7.836)
    49.04
    (80.97)
    86.10
    (69.76)
    79.59
    (63.46)
    70.31
    (22.00)
    Cmax at Cycle1 Day15
    95.14
    (12.79)
    245.8
    (13.45)
    241.1
    (30.90)
    225.0
    (9.213)
    292.7
    (33.84)
    321.8
    (23.05)
    Cmin at Cycle2 Day1
    23.83
    (14.35)
    83.76
    (34.29)
    89.20
    (56.00)
    136.3
    (45.72)
    124.8
    (55.78)
    142.5
    (50.52)
    78.41
    (55.62)
    Cmax at Cycle2 Day1
    84.43
    (17.13)
    280.9
    (12.48)
    297.5
    (42.41)
    267.0
    (25.97)
    370.9
    (42.57)
    342.3
    (18.08)
    258.1
    (28.36)
    27. Secondary Outcome
    Title Number of Participants With Positive Anti-drug Antibodies (ADA) to MEDI0680 in Dose-escalation and Dose-expansion Phases
    Description Number of participants with positive ADAs to MEDI0680 are reported. 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. Transient positive is defined as negative at last post-baseline assessment and positive at only one post-baseline assessment or at >=2 post-baseline assessments (with <16 weeks between first and last positive).
    Time Frame Cycle 1 Day 1, Cycle 2 Day 1, Cycle 5 Day 1, Cycle 8 Day 1, Cycle 11 Day 1, 90 and 180 days post end of treatment (approximately 5 years and 10 months)

    Outcome Measure Data

    Analysis Population Description
    As-treated population included those participants who received MEDI0680 and grouped according to actual treatment received. The "Number of participants Analyzed" denotes the number of participants evaluated for this outcome measure.
    Arm/Group Title MEDI0680 0.1 mg/kg + Durvalumab 3 mg MEDI0680 0.1 mg/kg + Durvalumab 10 mg MEDI0680 0.5 mg/kg + Durvalumab 10 mg MEDI0680 2.5 mg/kg + Durvalumab 10 mg MEDI0680 10 mg/kg + Durvalumab 10 mg MEDI0680 20 mg/kg + Durvalumab 10 mg MEDI0680 20 mg/kg MEDI0680 20 mg/kg + Durvalumab 750 mg
    Arm/Group Description Participants in dose-escalation phase received IV infusion of MEDI0680 0.1 mg/kg and durvalumab 3 mg/kg every 2 weeks (Q2W) for up to 12 months. Participants in dose-escalation phase received IV infusion of MEDI0680 0.1 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months. Participants in dose-escalation phase received IV infusion of MEDI0680 0.5 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months. Participants in dose-escalation phase received IV infusion of MEDI0680 2.5 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months. Participants in dose-escalation phase received IV infusion of MEDI0680 10 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months. Participants in dose-escalation phase received IV infusion of MEDI0680 20 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months. Participants in dose-expansion phase received IV infusion of MEDI0680 20 mg/kg Q2W until unacceptable toxicity, confirmed disease progression, development of other reason for treatment discontinuation, or for a maximum of 2 years, whichever occurred first. Participants in dose-expansion phase received IV infusion of MEDI0680 20 mg/kg and durvalumab 750 mg/kg Q2W until unacceptable toxicity, confirmed disease progression, development of other reason for treatment discontinuation, or for a maximum of 2 years, whichever occurred first.
    Measure Participants 4 5 3 3 8 6 4 39
    ADA positive post-baseline
    2
    50%
    0
    0%
    2
    66.7%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    2
    4.8%
    Persistent Positive
    2
    50%
    0
    0%
    2
    66.7%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Transient Positive
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    2
    4.8%
    28. Secondary Outcome
    Title Number of Participants With Positive ADA to Durvalumab in Dose-escalation and Dose-expansion Phases
    Description Number of participants with positive ADA to durvalumab are reported. 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. Transient positive is defined as negative at last post-baseline assessment and positive at only one post-baseline assessment or at >=2 post-baseline assessments (with <16 weeks between first and last positive).
    Time Frame Cycle 1 Day 1, Cycle 2 Day 1, Cycle 5 Day 1, Cycle 8 Day 1, Cycle 11 Day 1, 90 and 180 days post end of treatment (approximately 5 years and 10 months)

    Outcome Measure Data

    Analysis Population Description
    As-treated population included those participants who received durvalumab and grouped according to actual treatment received. The "Number of participants Analyzed" denotes the number of participants evaluated for this outcome measure.
    Arm/Group Title MEDI0680 0.1 mg/kg + Durvalumab 3 mg MEDI0680 0.1 mg/kg + Durvalumab 10 mg MEDI0680 0.5 mg/kg + Durvalumab 10 mg MEDI0680 2.5 mg/kg + Durvalumab 10 mg MEDI0680 10 mg/kg + Durvalumab 10 mg MEDI0680 20 mg/kg + Durvalumab 10 mg MEDI0680 20 mg/kg + Durvalumab 750 mg
    Arm/Group Description Participants in dose-escalation phase received IV infusion of MEDI0680 0.1 mg/kg and durvalumab 3 mg/kg every 2 weeks (Q2W) for up to 12 months. Participants in dose-escalation phase received IV infusion of MEDI0680 0.1 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months. Participants in dose-escalation phase received IV infusion of MEDI0680 0.5 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months. Participants in dose-escalation phase received IV infusion of MEDI0680 2.5 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months. Participants in dose-escalation phase received IV infusion of MEDI0680 10 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months. Participants in dose-escalation phase received IV infusion of MEDI0680 20 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months. Participants in dose-expansion phase received IV infusion of MEDI0680 20 mg/kg and durvalumab 750 mg/kg Q2W until unacceptable toxicity, confirmed disease progression, development of other reason for treatment discontinuation, or for a maximum of 2 years, whichever occurred first.
    Measure Participants 4 5 3 3 8 6 39
    ADA positive post-baseline
    1
    25%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    2
    50%
    Persistent Positive
    1
    25%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    2
    50%
    Transient Positive
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    29. Secondary Outcome
    Title ORR for Participants With Programmed Cell Death Ligand 1 (PD-L1) Status Positive and Negative in Dose-expansion Phase
    Description ORR for participants with PD-L1 status positive and negative are reported. The ORR is defined as best overall response 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. The PR is defined as >= 30% decrease in the sum of diameters of target lesions (compared to baseline) and no new non-target lesion. A confirmed CR or PR is defined as 2 CRs or 2 PRs that were separated by at least 4 weeks with no evidence of progression in-between.
    Time Frame From baseline (Day -42 to Day -1) through disease progression or end of treatment (approximately 5 years 10 months)

    Outcome Measure Data

    Analysis Population Description
    As-treated population included those participants who received any study drug (MEDI0680, durvalumab, or nivolumab) and grouped according to actual treatment received. Participants with PD-L1 positive (> 1% tumor cell membrane or > 1% immune cell staining) and PD-L1 negative (<= 1% tumor cell membrane and <= 1% immune cell staining) were evaluated for this outcome measure.
    Arm/Group Title MEDI0680 20 mg/kg MEDI0680 20 mg/kg + Durvalumab 750 mg Nivolumab 240 mg
    Arm/Group Description Participants in dose-expansion phase received IV infusion of MEDI0680 20 mg/kg Q2W until unacceptable toxicity, confirmed disease progression, development of other reason for treatment discontinuation, or for a maximum of 2 years, whichever occurred first. Participants in dose-expansion phase received IV infusion of MEDI0680 20 mg/kg and durvalumab 750 mg/kg Q2W until unacceptable toxicity, confirmed disease progression, development of other reason for treatment discontinuation, or for a maximum of 2 years, whichever occurred first. Participants in dose-expansion phase received IV infusion of nivolumab 240 mg Q2W until unacceptable toxicity, confirmed disease progression, development of other reason for treatment discontinuation, or for a maximum of 2 years, whichever occurred first.
    Measure Participants 4 42 21
    Participants with PD-L1 positive
    0
    0%
    40.0
    800%
    37.5
    1250%
    Participants with PD-L1 negative
    0
    0%
    13.5
    270%
    15.4
    513.3%

    Adverse Events

    Time Frame Day 1 through 90 days post end of treatment (approximately 5 years 10 months)
    Adverse Event Reporting Description
    Arm/Group Title MEDI0680 0.1 mg/kg + Durvalumab 3 mg MEDI0680 0.1 mg/kg + Durvalumab 10 mg MEDI0680 0.5 mg/kg + Durvalumab 10 mg MEDI0680 2.5 mg/kg + Durvalumab 10 mg MEDI0680 10 mg/kg + Durvalumab 10 mg MEDI0680 20 mg/kg + Durvalumab 10 mg MEDI0680 20 mg/kg MEDI0680 20 mg/kg + Durvalumab 750 mg Nivolumab 240 mg
    Arm/Group Description Participants in dose-escalation phase received IV infusion of MEDI0680 0.1 mg/kg and durvalumab 3 mg/kg Q2W for up to 12 months. Participants in dose-escalation phase received IV infusion of MEDI0680 0.1 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months. Participants in dose-escalation phase received IV infusion of MEDI0680 0.5 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months. Participants in dose-escalation phase received IV infusion of MEDI0680 2.5 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months. Participants in dose-escalation phase received IV infusion of MEDI0680 10 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months. Participants in dose-escalation phase received IV infusion of MEDI0680 20 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months. Participants in dose-expansion phase received IV infusion of MEDI0680 20 mg/kg Q2W until unacceptable toxicity, confirmed disease progression, development of other reason for treatment discontinuation, or for a maximum of 2 years, whichever occurred first. Participants in dose-expansion phase received IV infusion of MEDI0680 20 mg/kg and durvalumab 750 mg/kg Q2W until unacceptable toxicity, confirmed disease progression, development of other reason for treatment discontinuation, or for a maximum of 2 years, whichever occurred first. Participants in dose-expansion phase received IV infusion of nivolumab 240 mg Q2W until unacceptable toxicity, confirmed disease progression, development of other reason for treatment discontinuation, or for a maximum of 2 years, whichever occurred first.
    All Cause Mortality
    MEDI0680 0.1 mg/kg + Durvalumab 3 mg MEDI0680 0.1 mg/kg + Durvalumab 10 mg MEDI0680 0.5 mg/kg + Durvalumab 10 mg MEDI0680 2.5 mg/kg + Durvalumab 10 mg MEDI0680 10 mg/kg + Durvalumab 10 mg MEDI0680 20 mg/kg + Durvalumab 10 mg MEDI0680 20 mg/kg MEDI0680 20 mg/kg + Durvalumab 750 mg Nivolumab 240 mg
    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 2/4 (50%) 2/5 (40%) 1/3 (33.3%) 2/3 (66.7%) 5/9 (55.6%) 1/6 (16.7%) 2/4 (50%) 9/42 (21.4%) 4/21 (19%)
    Serious Adverse Events
    MEDI0680 0.1 mg/kg + Durvalumab 3 mg MEDI0680 0.1 mg/kg + Durvalumab 10 mg MEDI0680 0.5 mg/kg + Durvalumab 10 mg MEDI0680 2.5 mg/kg + Durvalumab 10 mg MEDI0680 10 mg/kg + Durvalumab 10 mg MEDI0680 20 mg/kg + Durvalumab 10 mg MEDI0680 20 mg/kg MEDI0680 20 mg/kg + Durvalumab 750 mg Nivolumab 240 mg
    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%) 1/5 (20%) 1/3 (33.3%) 2/3 (66.7%) 6/9 (66.7%) 0/6 (0%) 3/4 (75%) 22/42 (52.4%) 13/21 (61.9%)
    Cardiac disorders
    Atrial fibrillation 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/9 (11.1%) 1 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 0/21 (0%) 0
    Pericardial effusion 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/9 (11.1%) 1 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 0/21 (0%) 0
    Endocrine disorders
    Adrenal insufficiency 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 1/21 (4.8%) 1
    Hypercalcaemia of malignancy 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 0/21 (0%) 0
    Hyperthyroidism 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/9 (11.1%) 1 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 0/21 (0%) 0
    Hypothyroidism 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/9 (11.1%) 1 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 0/21 (0%) 0
    Eye disorders
    Eye pain 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 0/21 (0%) 0
    Gastrointestinal disorders
    Abdominal pain 1/4 (25%) 1 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 1/4 (25%) 1 0/42 (0%) 0 2/21 (9.5%) 3
    Colitis microscopic 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 2 0/21 (0%) 0
    Diarrhoea 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 1/21 (4.8%) 2
    Haematemesis 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/9 (11.1%) 1 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 0/21 (0%) 0
    Immune-mediated enterocolitis 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 0/21 (0%) 0
    Immune-mediated pancreatitis 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 0/21 (0%) 0
    Pancreatitis 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 0/21 (0%) 0
    Small intestinal obstruction 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/9 (11.1%) 1 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 0/21 (0%) 0
    Vomiting 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/9 (11.1%) 1 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 0/21 (0%) 0
    General disorders
    Chest pain 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 0/21 (0%) 0
    Chills 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 0/21 (0%) 0
    Fatigue 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 0/21 (0%) 0
    Pain 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 1/21 (4.8%) 1
    Pyrexia 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 2/42 (4.8%) 4 0/21 (0%) 0
    Hepatobiliary disorders
    Cholecystitis 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 1/4 (25%) 1 0/42 (0%) 0 0/21 (0%) 0
    Hepatic haemorrhage 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 1/21 (4.8%) 1
    Hepatocellular injury 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 0/21 (0%) 0
    Infections and infestations
    Cellulitis 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 0/21 (0%) 0
    Device related infection 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 0/21 (0%) 0
    Osteomyelitis 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 0/21 (0%) 0
    Postoperative wound infection 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 1/21 (4.8%) 1
    Spinal cord infection 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 0/21 (0%) 0
    Urinary tract infection 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/9 (11.1%) 1 0/6 (0%) 0 1/4 (25%) 1 0/42 (0%) 0 0/21 (0%) 0
    Injury, poisoning and procedural complications
    Hip fracture 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 2 0/21 (0%) 0
    Infusion related reaction 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 2 0/21 (0%) 0
    Investigations
    Alanine aminotransferase increased 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 0/21 (0%) 0
    Aspartate aminotransferase increased 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 0/21 (0%) 0
    Electrocardiogram qt prolonged 0/4 (0%) 0 0/5 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 0/21 (0%) 0
    Transaminases increased 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 0/21 (0%) 0
    Metabolism and nutrition disorders
    Dehydration 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 0/21 (0%) 0
    Failure to thrive 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 1/21 (4.8%) 1
    Hypercalcaemia 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 2/42 (4.8%) 2 0/21 (0%) 0
    Hyponatraemia 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 1/4 (25%) 1 0/42 (0%) 0 0/21 (0%) 0
    Musculoskeletal and connective tissue disorders
    Arthralgia 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 0/21 (0%) 0
    Back pain 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 2/42 (4.8%) 2 0/21 (0%) 0
    Bone pain 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 3/21 (14.3%) 5
    Myalgia 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 0/21 (0%) 0
    Pain in extremity 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 1/21 (4.8%) 1
    Pathological fracture 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 1/4 (25%) 1 0/42 (0%) 0 1/21 (4.8%) 1
    Spinal pain 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 0/21 (0%) 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Metastases to bone 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 0/21 (0%) 0
    Metastases to central nervous system 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 1/4 (25%) 1 0/42 (0%) 0 0/21 (0%) 0
    Squamous cell carcinoma of skin 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 1/21 (4.8%) 1
    Nervous system disorders
    Aphasia 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 1/21 (4.8%) 1
    Cerebrospinal fluid leakage 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 1/21 (4.8%) 1
    Cerebrovascular accident 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 1/21 (4.8%) 1
    Encephalitis autoimmune 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 0/21 (0%) 0
    Haemorrhage intracranial 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/9 (11.1%) 1 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 1/21 (4.8%) 1
    Headache 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 0/21 (0%) 0
    Intracranial mass 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/9 (11.1%) 1 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 0/21 (0%) 0
    Seizure 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 1/4 (25%) 1 0/42 (0%) 0 0/21 (0%) 0
    Psychiatric disorders
    Mental status changes 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 0/21 (0%) 0
    Reproductive system and breast disorders
    Benign prostatic hyperplasia 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 0/21 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Chronic obstructive pulmonary disease 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 0/21 (0%) 0
    Dyspnoea 0/4 (0%) 0 1/5 (20%) 1 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 1/21 (4.8%) 1
    Haemoptysis 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 1/21 (4.8%) 2
    Pleural effusion 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 2/9 (22.2%) 2 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 0/21 (0%) 0
    Skin and subcutaneous tissue disorders
    Diabetic foot 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 2 0/21 (0%) 0
    Rash maculo-papular 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 0/21 (0%) 0
    Rash papular 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 0/21 (0%) 0
    Vascular disorders
    Hypotension 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 1/21 (4.8%) 1
    Peripheral ischaemia 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 0/21 (0%) 0
    Other (Not Including Serious) Adverse Events
    MEDI0680 0.1 mg/kg + Durvalumab 3 mg MEDI0680 0.1 mg/kg + Durvalumab 10 mg MEDI0680 0.5 mg/kg + Durvalumab 10 mg MEDI0680 2.5 mg/kg + Durvalumab 10 mg MEDI0680 10 mg/kg + Durvalumab 10 mg MEDI0680 20 mg/kg + Durvalumab 10 mg MEDI0680 20 mg/kg MEDI0680 20 mg/kg + Durvalumab 750 mg Nivolumab 240 mg
    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%) 5/5 (100%) 3/3 (100%) 3/3 (100%) 9/9 (100%) 6/6 (100%) 4/4 (100%) 41/42 (97.6%) 20/21 (95.2%)
    Blood and lymphatic system disorders
    Anaemia 0/4 (0%) 0 0/5 (0%) 0 1/3 (33.3%) 2 1/3 (33.3%) 1 3/9 (33.3%) 5 0/6 (0%) 0 1/4 (25%) 2 6/42 (14.3%) 10 5/21 (23.8%) 29
    Iron deficiency anaemia 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/9 (11.1%) 1 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 0/21 (0%) 0
    Leukocytosis 1/4 (25%) 1 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 0/21 (0%) 0
    Lymphopenia 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/9 (11.1%) 2 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 0/21 (0%) 0
    Neutropenia 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 0/21 (0%) 0
    Cardiac disorders
    Angina pectoris 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 1/4 (25%) 1 1/42 (2.4%) 1 0/21 (0%) 0
    Atrial fibrillation 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/9 (11.1%) 1 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 1/21 (4.8%) 1
    Cardiac failure congestive 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 1/21 (4.8%) 1
    Palpitations 1/4 (25%) 1 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 0/21 (0%) 0
    Sinus tachycardia 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/9 (11.1%) 1 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 0/21 (0%) 0
    Tachycardia 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 1/6 (16.7%) 1 0/4 (0%) 0 1/42 (2.4%) 1 0/21 (0%) 0
    Ear and labyrinth disorders
    Ear discomfort 0/4 (0%) 0 1/5 (20%) 1 1/3 (33.3%) 1 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 0/21 (0%) 0
    Ear disorder 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 0/21 (0%) 0
    Ear pain 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 1/6 (16.7%) 1 0/4 (0%) 0 1/42 (2.4%) 1 0/21 (0%) 0
    Hypoacusis 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 0/21 (0%) 0
    Tinnitus 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 0/21 (0%) 0
    Endocrine disorders
    Adrenal insufficiency 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 1/4 (25%) 1 1/42 (2.4%) 2 0/21 (0%) 0
    Hypercalcaemia of malignancy 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 4 0/21 (0%) 0
    Hyperthyroidism 0/4 (0%) 0 1/5 (20%) 1 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 1/4 (25%) 1 1/42 (2.4%) 1 1/21 (4.8%) 1
    Hypothyroidism 0/4 (0%) 0 2/5 (40%) 3 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 1/6 (16.7%) 1 1/4 (25%) 1 4/42 (9.5%) 4 2/21 (9.5%) 2
    Eye disorders
    Asthenopia 1/4 (25%) 1 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 0/21 (0%) 0
    Conjunctival haemorrhage 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 0/21 (0%) 0
    Conjunctivitis allergic 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 0/21 (0%) 0
    Diplopia 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 1/4 (25%) 1 0/42 (0%) 0 0/21 (0%) 0
    Dry eye 0/4 (0%) 0 0/5 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 0/21 (0%) 0
    Episcleritis 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 0/21 (0%) 0
    Eye irritation 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 2/9 (22.2%) 2 0/6 (0%) 0 0/4 (0%) 0 2/42 (4.8%) 2 0/21 (0%) 0
    Eye pain 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 1/21 (4.8%) 1
    Eye pruritus 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 2/42 (4.8%) 2 0/21 (0%) 0
    Eyelid ptosis 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 1/4 (25%) 1 0/42 (0%) 0 0/21 (0%) 0
    Keratitis 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 0/21 (0%) 0
    Lacrimation increased 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 1/6 (16.7%) 2 0/4 (0%) 0 2/42 (4.8%) 2 1/21 (4.8%) 1
    Ocular hyperaemia 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 1/21 (4.8%) 1
    Periorbital swelling 0/4 (0%) 0 1/5 (20%) 1 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 0/21 (0%) 0
    Photophobia 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 1/4 (25%) 1 0/42 (0%) 0 1/21 (4.8%) 2
    Vision blurred 0/4 (0%) 0 0/5 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/9 (0%) 0 1/6 (16.7%) 1 1/4 (25%) 1 0/42 (0%) 0 0/21 (0%) 0
    Visual impairment 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 0/21 (0%) 0
    Gastrointestinal disorders
    Abdominal discomfort 0/4 (0%) 0 1/5 (20%) 1 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 0/21 (0%) 0
    Abdominal distension 0/4 (0%) 0 1/5 (20%) 1 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 3/42 (7.1%) 4 0/21 (0%) 0
    Abdominal mass 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 0/21 (0%) 0
    Abdominal pain 1/4 (25%) 2 1/5 (20%) 2 0/3 (0%) 0 0/3 (0%) 0 1/9 (11.1%) 1 0/6 (0%) 0 0/4 (0%) 0 4/42 (9.5%) 5 3/21 (14.3%) 4
    Abdominal pain lower 0/4 (0%) 0 0/5 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 1/21 (4.8%) 2
    Abdominal pain upper 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/9 (11.1%) 1 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 2 1/21 (4.8%) 1
    Aphthous ulcer 0/4 (0%) 0 0/5 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 0/21 (0%) 0
    Ascites 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 1/21 (4.8%) 3
    Colitis 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 2/42 (4.8%) 3 0/21 (0%) 0
    Constipation 1/4 (25%) 1 2/5 (40%) 2 0/3 (0%) 0 1/3 (33.3%) 1 0/9 (0%) 0 2/6 (33.3%) 2 0/4 (0%) 0 12/42 (28.6%) 16 6/21 (28.6%) 7
    Diarrhoea 1/4 (25%) 3 2/5 (40%) 3 0/3 (0%) 0 0/3 (0%) 0 3/9 (33.3%) 12 5/6 (83.3%) 5 0/4 (0%) 0 15/42 (35.7%) 23 9/21 (42.9%) 14
    Dry mouth 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 2/42 (4.8%) 4 3/21 (14.3%) 3
    Duodenitis 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 0/21 (0%) 0
    Dyspepsia 1/4 (25%) 1 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 3/21 (14.3%) 5
    Dysphagia 1/4 (25%) 1 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 1/21 (4.8%) 1
    Epigastric discomfort 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 0/21 (0%) 0
    Faeces soft 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 3 0/21 (0%) 0
    Flatulence 1/4 (25%) 2 1/5 (20%) 1 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 1/6 (16.7%) 1 0/4 (0%) 0 3/42 (7.1%) 3 0/21 (0%) 0
    Gastrointestinal haemorrhage 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 1/21 (4.8%) 1
    Gastrooesophageal reflux disease 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 0/21 (0%) 0
    Gingival bleeding 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 2/21 (9.5%) 2
    Gingival pain 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/9 (11.1%) 1 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 0/21 (0%) 0
    Haemorrhoids 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 1/21 (4.8%) 1
    Immune-mediated enterocolitis 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 0/21 (0%) 0
    Inguinal hernia 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 0/21 (0%) 0
    Nausea 1/4 (25%) 3 1/5 (20%) 1 1/3 (33.3%) 1 2/3 (66.7%) 3 5/9 (55.6%) 7 1/6 (16.7%) 3 3/4 (75%) 4 10/42 (23.8%) 13 7/21 (33.3%) 8
    Odynophagia 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 0/21 (0%) 0
    Oral disorder 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 2/42 (4.8%) 2 0/21 (0%) 0
    Oral pain 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 2/9 (22.2%) 2 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 1/21 (4.8%) 1
    Pancreatitis 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 1/21 (4.8%) 1
    Rectal haemorrhage 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 3/42 (7.1%) 4 0/21 (0%) 0
    Stomatitis 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 2/21 (9.5%) 2
    Vomiting 0/4 (0%) 0 1/5 (20%) 2 0/3 (0%) 0 1/3 (33.3%) 1 2/9 (22.2%) 2 2/6 (33.3%) 2 1/4 (25%) 1 11/42 (26.2%) 15 6/21 (28.6%) 8
    General disorders
    Asthenia 1/4 (25%) 1 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 1/4 (25%) 1 5/42 (11.9%) 7 1/21 (4.8%) 1
    Axillary pain 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 0/21 (0%) 0
    Catheter site pruritus 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/9 (11.1%) 1 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 0/21 (0%) 0
    Chest pain 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 1/4 (25%) 1 2/42 (4.8%) 2 0/21 (0%) 0
    Chills 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/9 (11.1%) 1 0/6 (0%) 0 0/4 (0%) 0 3/42 (7.1%) 3 2/21 (9.5%) 2
    Cyst 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 0/21 (0%) 0
    Facial pain 0/4 (0%) 0 0/5 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 0/21 (0%) 0
    Fatigue 1/4 (25%) 2 3/5 (60%) 3 1/3 (33.3%) 1 1/3 (33.3%) 1 2/9 (22.2%) 2 2/6 (33.3%) 3 4/4 (100%) 4 19/42 (45.2%) 25 6/21 (28.6%) 7
    Feeling hot 1/4 (25%) 1 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 0/21 (0%) 0
    Gait disturbance 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 2/21 (9.5%) 2
    Inflammation 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 0/21 (0%) 0
    Influenza like illness 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 1/6 (16.7%) 2 0/4 (0%) 0 0/42 (0%) 0 1/21 (4.8%) 1
    Infusion site pain 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 0/21 (0%) 0
    Malaise 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/9 (11.1%) 1 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 1/21 (4.8%) 1
    Mass 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 0/21 (0%) 0
    Mucosal inflammation 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 1/6 (16.7%) 3 0/4 (0%) 0 2/42 (4.8%) 2 1/21 (4.8%) 1
    Nodule 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/9 (11.1%) 1 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 0/21 (0%) 0
    Non-cardiac chest pain 0/4 (0%) 0 0/5 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 1/4 (25%) 1 1/42 (2.4%) 1 0/21 (0%) 0
    Oedema 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 1/4 (25%) 1 1/42 (2.4%) 1 2/21 (9.5%) 2
    Oedema peripheral 1/4 (25%) 2 0/5 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 3/9 (33.3%) 5 0/6 (0%) 0 1/4 (25%) 1 5/42 (11.9%) 7 3/21 (14.3%) 4
    Pain 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 3/42 (7.1%) 3 0/21 (0%) 0
    Pyrexia 0/4 (0%) 0 0/5 (0%) 0 2/3 (66.7%) 2 0/3 (0%) 0 3/9 (33.3%) 3 1/6 (16.7%) 1 2/4 (50%) 2 8/42 (19%) 12 2/21 (9.5%) 3
    Secretion discharge 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 0/21 (0%) 0
    Temperature intolerance 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/9 (11.1%) 1 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 0/21 (0%) 0
    Hepatobiliary disorders
    Cholelithiasis 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 1/4 (25%) 1 0/42 (0%) 0 0/21 (0%) 0
    Hepatocellular injury 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 0/21 (0%) 0
    Hepatotoxicity 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 1/21 (4.8%) 1
    Liver disorder 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 0/21 (0%) 0
    Immune system disorders
    Allergy to arthropod sting 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 2 0/21 (0%) 0
    Contrast media reaction 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 0/21 (0%) 0
    Infections and infestations
    Abscess 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 1/6 (16.7%) 1 0/4 (0%) 0 0/42 (0%) 0 0/21 (0%) 0
    Bronchiolitis 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 0/21 (0%) 0
    Bronchitis 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 2 0/21 (0%) 0
    Conjunctivitis 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/9 (11.1%) 1 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 0/21 (0%) 0
    Ear infection 2/4 (50%) 3 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 0/21 (0%) 0
    Eye infection 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 1/21 (4.8%) 1
    Gastrointestinal fungal infection 0/4 (0%) 0 1/5 (20%) 1 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 0/21 (0%) 0
    Gingivitis 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 1/21 (4.8%) 1
    Herpes zoster 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/9 (11.1%) 1 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 0/21 (0%) 0
    Hordeolum 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 0/21 (0%) 0
    Influenza 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/9 (11.1%) 1 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 0/21 (0%) 0
    Kidney infection 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 2 0/21 (0%) 0
    Lower respiratory tract infection 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 1/21 (4.8%) 1
    Lower respiratory tract infection bacterial 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 0/21 (0%) 0
    Nasopharyngitis 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/9 (11.1%) 1 0/6 (0%) 0 0/4 (0%) 0 3/42 (7.1%) 3 0/21 (0%) 0
    Oral candidiasis 0/4 (0%) 0 1/5 (20%) 1 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 0/21 (0%) 0
    Oral fungal infection 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 0/21 (0%) 0
    Oral herpes 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 2/42 (4.8%) 2 0/21 (0%) 0
    Otitis media 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 0/21 (0%) 0
    Pneumonia 0/4 (0%) 0 1/5 (20%) 1 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 0/21 (0%) 0
    Rash pustular 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 0/21 (0%) 0
    Respiratory tract infection 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 1/21 (4.8%) 2
    Rhinitis 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 0/21 (0%) 0
    Sinusitis 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 2/21 (9.5%) 3
    Tooth abscess 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 1/21 (4.8%) 1
    Tooth infection 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 1/21 (4.8%) 1
    Upper respiratory tract infection 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 2/9 (22.2%) 3 3/6 (50%) 4 0/4 (0%) 0 3/42 (7.1%) 5 0/21 (0%) 0
    Urinary tract infection 0/4 (0%) 0 1/5 (20%) 1 0/3 (0%) 0 1/3 (33.3%) 2 1/9 (11.1%) 1 0/6 (0%) 0 1/4 (25%) 1 2/42 (4.8%) 2 4/21 (19%) 5
    Viral infection 0/4 (0%) 0 1/5 (20%) 1 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 1/21 (4.8%) 1
    Viral upper respiratory tract infection 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 1/6 (16.7%) 1 0/4 (0%) 0 0/42 (0%) 0 0/21 (0%) 0
    Injury, poisoning and procedural complications
    Anaemia postoperative 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 1/21 (4.8%) 1
    Arthropod bite 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 1/21 (4.8%) 1
    Chemical burn of skin 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 0/21 (0%) 0
    Contusion 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 2/6 (33.3%) 3 1/4 (25%) 1 0/42 (0%) 0 0/21 (0%) 0
    Cystitis radiation 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 1/4 (25%) 2 0/42 (0%) 0 0/21 (0%) 0
    Fall 0/4 (0%) 0 1/5 (20%) 1 0/3 (0%) 0 1/3 (33.3%) 2 1/9 (11.1%) 1 2/6 (33.3%) 2 0/4 (0%) 0 2/42 (4.8%) 2 0/21 (0%) 0
    Humerus fracture 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 1/21 (4.8%) 1
    Infusion related reaction 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 4/42 (9.5%) 4 1/21 (4.8%) 1
    Post procedural oedema 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 1/21 (4.8%) 1
    Procedural pain 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/9 (11.1%) 1 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 0/21 (0%) 0
    Radiation skin injury 0/4 (0%) 0 0/5 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 0/21 (0%) 0
    Rib fracture 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 1/6 (16.7%) 1 0/4 (0%) 0 1/42 (2.4%) 1 0/21 (0%) 0
    Scratch 0/4 (0%) 0 1/5 (20%) 1 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 0/21 (0%) 0
    Skin abrasion 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 3/42 (7.1%) 4 1/21 (4.8%) 1
    Spinal compression fracture 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 1/21 (4.8%) 1
    Sunburn 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 1/21 (4.8%) 1
    Wound 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 0/21 (0%) 0
    Investigations
    Activated partial thromboplastin time prolonged 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 1/6 (16.7%) 1 0/4 (0%) 0 0/42 (0%) 0 0/21 (0%) 0
    Alanine aminotransferase increased 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/9 (11.1%) 5 0/6 (0%) 0 1/4 (25%) 1 1/42 (2.4%) 3 3/21 (14.3%) 3
    Amylase decreased 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 1/21 (4.8%) 1
    Amylase increased 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/9 (11.1%) 1 1/6 (16.7%) 1 1/4 (25%) 1 3/42 (7.1%) 6 3/21 (14.3%) 8
    Aspartate aminotransferase increased 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 2/9 (22.2%) 4 0/6 (0%) 0 1/4 (25%) 1 2/42 (4.8%) 14 3/21 (14.3%) 3
    Blood alkaline phosphatase increased 1/4 (25%) 3 0/5 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 1/9 (11.1%) 1 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 1/21 (4.8%) 1
    Blood bilirubin increased 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 1/21 (4.8%) 1
    Blood creatine increased 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 1/4 (25%) 1 1/42 (2.4%) 1 0/21 (0%) 0
    Blood creatine phosphokinase increased 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 0/21 (0%) 0
    Blood creatinine increased 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 2/9 (22.2%) 3 1/6 (16.7%) 1 1/4 (25%) 1 4/42 (9.5%) 5 3/21 (14.3%) 6
    Blood fibrinogen decreased 1/4 (25%) 1 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 1/6 (16.7%) 1 0/4 (0%) 0 0/42 (0%) 0 0/21 (0%) 0
    Blood glucose increased 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 1/21 (4.8%) 1
    Blood iron decreased 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 1/21 (4.8%) 1
    Blood phosphorus decreased 1/4 (25%) 1 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 0/21 (0%) 0
    Blood testosterone decreased 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 1/21 (4.8%) 1
    Blood thyroid stimulating hormone increased 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 2/42 (4.8%) 2 2/21 (9.5%) 2
    Blood triglycerides increased 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 2 1/21 (4.8%) 3
    Blood urea increased 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/9 (11.1%) 1 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 0/21 (0%) 0
    Blood urine present 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 1/21 (4.8%) 1
    C-reactive protein increased 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 2 1/21 (4.8%) 1
    Eastern cooperative oncology group performance status worsened 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 0/21 (0%) 0
    Electrocardiogram qt prolonged 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 1/4 (25%) 1 1/42 (2.4%) 1 0/21 (0%) 0
    Electrocardiogram t wave abnormal 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 1/21 (4.8%) 1
    Gamma-glutamyltransferase increased 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/9 (11.1%) 1 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 0/21 (0%) 0
    General physical condition abnormal 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 2/42 (4.8%) 2 0/21 (0%) 0
    Influenza b virus test positive 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 0/21 (0%) 0
    International normalised ratio increased 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 1/6 (16.7%) 1 0/4 (0%) 0 0/42 (0%) 0 0/21 (0%) 0
    Lipase increased 1/4 (25%) 2 0/5 (0%) 0 1/3 (33.3%) 3 0/3 (0%) 0 1/9 (11.1%) 5 0/6 (0%) 0 1/4 (25%) 2 4/42 (9.5%) 19 2/21 (9.5%) 12
    Lymphocyte count decreased 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 1/6 (16.7%) 1 0/4 (0%) 0 0/42 (0%) 0 1/21 (4.8%) 1
    Neutrophil count decreased 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 1/4 (25%) 1 1/42 (2.4%) 3 0/21 (0%) 0
    Platelet count decreased 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 1/21 (4.8%) 2
    Platelet count increased 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 1/21 (4.8%) 1
    Procalcitonin increased 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 0/21 (0%) 0
    Prothrombin time prolonged 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 1/6 (16.7%) 1 0/4 (0%) 0 0/42 (0%) 0 1/21 (4.8%) 1
    Serum ferritin decreased 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 1/21 (4.8%) 1
    Tri-iodothyronine free abnormal 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 1/21 (4.8%) 1
    Weight decreased 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/9 (11.1%) 1 1/6 (16.7%) 1 0/4 (0%) 0 5/42 (11.9%) 7 0/21 (0%) 0
    Weight increased 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 3/42 (7.1%) 3 0/21 (0%) 0
    White blood cell count decreased 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 1/6 (16.7%) 2 0/4 (0%) 0 0/42 (0%) 0 0/21 (0%) 0
    White blood cell count increased 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 1/21 (4.8%) 1
    Metabolism and nutrition disorders
    Acidosis 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 1/21 (4.8%) 1
    Decreased appetite 1/4 (25%) 2 1/5 (20%) 1 2/3 (66.7%) 2 0/3 (0%) 0 2/9 (22.2%) 2 2/6 (33.3%) 4 0/4 (0%) 0 5/42 (11.9%) 5 1/21 (4.8%) 1
    Dehydration 1/4 (25%) 1 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/9 (11.1%) 1 1/6 (16.7%) 1 0/4 (0%) 0 2/42 (4.8%) 3 1/21 (4.8%) 2
    Glucose tolerance impaired 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 1/21 (4.8%) 1
    Gout 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 1/21 (4.8%) 1
    Hypercalcaemia 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/9 (11.1%) 1 1/6 (16.7%) 1 0/4 (0%) 0 6/42 (14.3%) 9 2/21 (9.5%) 2
    Hyperglycaemia 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/9 (11.1%) 1 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 0/21 (0%) 0
    Hyperkalaemia 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/9 (11.1%) 3 0/6 (0%) 0 0/4 (0%) 0 2/42 (4.8%) 3 2/21 (9.5%) 5
    Hypermagnesaemia 0/4 (0%) 0 0/5 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 0/21 (0%) 0
    Hypertriglyceridaemia 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 0/21 (0%) 0
    Hyperuricaemia 1/4 (25%) 1 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/9 (11.1%) 1 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 0/21 (0%) 0
    Hypoalbuminaemia 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/9 (11.1%) 1 0/6 (0%) 0 0/4 (0%) 0 2/42 (4.8%) 3 0/21 (0%) 0
    Hypocalcaemia 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 0/21 (0%) 0
    Hypoglycaemia 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 0/21 (0%) 0
    Hypokalaemia 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 2/9 (22.2%) 4 0/6 (0%) 0 0/4 (0%) 0 5/42 (11.9%) 6 2/21 (9.5%) 2
    Hypomagnesaemia 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 2/9 (22.2%) 2 0/6 (0%) 0 0/4 (0%) 0 4/42 (9.5%) 9 2/21 (9.5%) 6
    Hyponatraemia 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 2/9 (22.2%) 3 1/6 (16.7%) 1 0/4 (0%) 0 3/42 (7.1%) 4 1/21 (4.8%) 5
    Hypophosphataemia 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 3/21 (14.3%) 8
    Metabolic alkalosis 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 1/21 (4.8%) 1
    Type 2 diabetes mellitus 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 2 0/21 (0%) 0
    Musculoskeletal and connective tissue disorders
    Arthralgia 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 2/9 (22.2%) 2 2/6 (33.3%) 2 1/4 (25%) 1 10/42 (23.8%) 18 7/21 (33.3%) 12
    Arthritis 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 2/6 (33.3%) 2 0/4 (0%) 0 0/42 (0%) 0 0/21 (0%) 0
    Back pain 1/4 (25%) 1 2/5 (40%) 2 0/3 (0%) 0 0/3 (0%) 0 2/9 (22.2%) 2 1/6 (16.7%) 1 1/4 (25%) 1 10/42 (23.8%) 11 2/21 (9.5%) 2
    Bone lesion 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 0/21 (0%) 0
    Flank pain 0/4 (0%) 0 0/5 (0%) 0 1/3 (33.3%) 1 1/3 (33.3%) 1 2/9 (22.2%) 2 1/6 (16.7%) 1 0/4 (0%) 0 4/42 (9.5%) 5 1/21 (4.8%) 1
    Groin pain 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 1/21 (4.8%) 1
    Joint range of motion decreased 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 1/6 (16.7%) 1 0/4 (0%) 0 0/42 (0%) 0 0/21 (0%) 0
    Joint swelling 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 0/21 (0%) 0
    Limb discomfort 0/4 (0%) 0 1/5 (20%) 1 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 0/21 (0%) 0
    Muscle spasms 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/9 (11.1%) 1 2/6 (33.3%) 4 0/4 (0%) 0 6/42 (14.3%) 6 2/21 (9.5%) 2
    Muscular weakness 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 3/21 (14.3%) 3
    Musculoskeletal chest pain 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 1/4 (25%) 1 4/42 (9.5%) 6 1/21 (4.8%) 1
    Musculoskeletal pain 1/4 (25%) 3 0/5 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/9 (0%) 0 2/6 (33.3%) 2 0/4 (0%) 0 5/42 (11.9%) 6 1/21 (4.8%) 1
    Musculoskeletal stiffness 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 1/21 (4.8%) 1
    Myalgia 2/4 (50%) 2 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/9 (11.1%) 2 0/6 (0%) 0 0/4 (0%) 0 6/42 (14.3%) 9 3/21 (14.3%) 3
    Neck pain 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 1/21 (4.8%) 1
    Osteoarthritis 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 0/21 (0%) 0
    Pain in extremity 0/4 (0%) 0 1/5 (20%) 1 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 2/6 (33.3%) 2 0/4 (0%) 0 6/42 (14.3%) 7 4/21 (19%) 5
    Pain in jaw 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 1/4 (25%) 1 0/42 (0%) 0 0/21 (0%) 0
    Pathological fracture 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 1/21 (4.8%) 1
    Spinal pain 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 0/21 (0%) 0
    Tendon disorder 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 0/21 (0%) 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Basal cell carcinoma 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 0/21 (0%) 0
    Oesophageal adenocarcinoma 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 1/21 (4.8%) 1
    Seborrhoeic keratosis 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 0/21 (0%) 0
    Squamous cell carcinoma 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 0/21 (0%) 0
    Tumour pain 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/9 (11.1%) 1 0/6 (0%) 0 0/4 (0%) 0 2/42 (4.8%) 2 0/21 (0%) 0
    Nervous system disorders
    Dizziness 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/9 (11.1%) 1 2/6 (33.3%) 3 1/4 (25%) 3 3/42 (7.1%) 3 4/21 (19%) 4
    Dysgeusia 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 1/4 (25%) 1 1/42 (2.4%) 1 0/21 (0%) 0
    Facial paralysis 1/4 (25%) 1 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 0/21 (0%) 0
    Head discomfort 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 1/21 (4.8%) 1
    Headache 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 4 2/9 (22.2%) 3 0/6 (0%) 0 1/4 (25%) 2 6/42 (14.3%) 7 5/21 (23.8%) 7
    Hyperaesthesia 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 0/21 (0%) 0
    Hypoaesthesia 0/4 (0%) 0 1/5 (20%) 1 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 2/42 (4.8%) 2 1/21 (4.8%) 1
    Hyposmia 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/9 (11.1%) 1 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 0/21 (0%) 0
    Lethargy 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 2/42 (4.8%) 2 1/21 (4.8%) 1
    Memory impairment 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 1/21 (4.8%) 1
    Neuralgia 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/9 (11.1%) 1 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 0/21 (0%) 0
    Neuropathy peripheral 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 1/6 (16.7%) 1 0/4 (0%) 0 0/42 (0%) 0 0/21 (0%) 0
    Paraesthesia 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 5/42 (11.9%) 6 1/21 (4.8%) 3
    Peripheral sensory neuropathy 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/9 (11.1%) 1 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 1/21 (4.8%) 2
    Sciatica 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 0/21 (0%) 0
    Sensory disturbance 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 1/21 (4.8%) 1
    Somnolence 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 3/42 (7.1%) 3 0/21 (0%) 0
    Tremor 2/4 (50%) 2 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 2 0/21 (0%) 0
    Psychiatric disorders
    Agitation 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 0/21 (0%) 0
    Anxiety 1/4 (25%) 1 1/5 (20%) 1 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 2/42 (4.8%) 2 2/21 (9.5%) 2
    Confusional state 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 1/21 (4.8%) 1
    Delirium 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 0/21 (0%) 0
    Depression 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/9 (11.1%) 1 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 2/21 (9.5%) 2
    Insomnia 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 5/42 (11.9%) 5 3/21 (14.3%) 3
    Mood altered 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/9 (11.1%) 1 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 0/21 (0%) 0
    Renal and urinary disorders
    Dysuria 0/4 (0%) 0 1/5 (20%) 1 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 2/42 (4.8%) 2 2/21 (9.5%) 2
    Micturition urgency 0/4 (0%) 0 1/5 (20%) 1 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 0/21 (0%) 0
    Nocturia 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 0/21 (0%) 0
    Pollakiuria 1/4 (25%) 1 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 2/42 (4.8%) 2 2/21 (9.5%) 2
    Proteinuria 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/9 (11.1%) 1 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 0/21 (0%) 0
    Renal tubular necrosis 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 1/21 (4.8%) 1
    Urinary incontinence 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 0/21 (0%) 0
    Urinary retention 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 0/21 (0%) 0
    Urinary tract pain 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 1/21 (4.8%) 1
    Urine abnormality 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 0/21 (0%) 0
    Reproductive system and breast disorders
    Breast mass 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/9 (11.1%) 1 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 0/21 (0%) 0
    Erectile dysfunction 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 1/21 (4.8%) 1
    Galactorrhoea 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/9 (11.1%) 1 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 0/21 (0%) 0
    Pruritus genital 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 1/21 (4.8%) 1
    Respiratory, thoracic and mediastinal disorders
    Chronic obstructive pulmonary disease 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 5 0/21 (0%) 0
    Cough 0/4 (0%) 0 1/5 (20%) 1 1/3 (33.3%) 1 0/3 (0%) 0 1/9 (11.1%) 1 3/6 (50%) 4 1/4 (25%) 2 9/42 (21.4%) 17 8/21 (38.1%) 9
    Dry throat 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 0/21 (0%) 0
    Dysphonia 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 2/42 (4.8%) 2 1/21 (4.8%) 1
    Dyspnoea 1/4 (25%) 1 1/5 (20%) 1 0/3 (0%) 0 0/3 (0%) 0 2/9 (22.2%) 3 0/6 (0%) 0 0/4 (0%) 0 7/42 (16.7%) 9 8/21 (38.1%) 10
    Dyspnoea exertional 1/4 (25%) 1 0/5 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 1/21 (4.8%) 1
    Epistaxis 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 1/6 (16.7%) 1 0/4 (0%) 0 2/42 (4.8%) 3 2/21 (9.5%) 3
    Haemoptysis 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 1/4 (25%) 2 1/42 (2.4%) 1 0/21 (0%) 0
    Hiccups 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 1/6 (16.7%) 1 0/4 (0%) 0 0/42 (0%) 0 0/21 (0%) 0
    Hypoxia 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 1/21 (4.8%) 1
    Laryngeal obstruction 0/4 (0%) 0 1/5 (20%) 1 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 0/21 (0%) 0
    Lung disorder 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 2/42 (4.8%) 2 0/21 (0%) 0
    Nasal congestion 1/4 (25%) 1 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/9 (11.1%) 1 1/6 (16.7%) 1 0/4 (0%) 0 2/42 (4.8%) 3 2/21 (9.5%) 2
    Oropharyngeal discomfort 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 0/21 (0%) 0
    Oropharyngeal pain 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/9 (11.1%) 2 0/6 (0%) 0 0/4 (0%) 0 2/42 (4.8%) 2 2/21 (9.5%) 2
    Painful respiration 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 2/42 (4.8%) 2 0/21 (0%) 0
    Paranasal sinus hypersecretion 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 0/21 (0%) 0
    Pleural effusion 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/9 (11.1%) 1 0/6 (0%) 0 0/4 (0%) 0 2/42 (4.8%) 2 1/21 (4.8%) 1
    Pneumonitis 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 2 1/21 (4.8%) 3
    Productive cough 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 2 1/9 (11.1%) 1 0/6 (0%) 0 0/4 (0%) 0 7/42 (16.7%) 8 2/21 (9.5%) 2
    Pulmonary haemorrhage 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 1/21 (4.8%) 1
    Rales 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 0/21 (0%) 0
    Rhinitis allergic 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 2/42 (4.8%) 2 0/21 (0%) 0
    Rhinorrhoea 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/9 (11.1%) 1 1/6 (16.7%) 2 0/4 (0%) 0 4/42 (9.5%) 7 2/21 (9.5%) 4
    Sinus congestion 1/4 (25%) 2 1/5 (20%) 1 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 0/21 (0%) 0
    Sneezing 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 2/42 (4.8%) 2 0/21 (0%) 0
    Upper-airway cough syndrome 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 0/21 (0%) 0
    Wheezing 1/4 (25%) 1 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 1/6 (16.7%) 1 0/4 (0%) 0 1/42 (2.4%) 1 0/21 (0%) 0
    Skin and subcutaneous tissue disorders
    Acne 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 1/21 (4.8%) 1
    Alopecia 1/4 (25%) 1 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 2/42 (4.8%) 2 0/21 (0%) 0
    Dermatitis 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 0/21 (0%) 0
    Dermatitis acneiform 0/4 (0%) 0 0/5 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 1/9 (11.1%) 1 0/6 (0%) 0 1/4 (25%) 1 0/42 (0%) 0 2/21 (9.5%) 2
    Diabetic foot 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 4 0/21 (0%) 0
    Dry skin 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 1/6 (16.7%) 1 0/4 (0%) 0 5/42 (11.9%) 5 4/21 (19%) 4
    Ecchymosis 1/4 (25%) 1 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 0/21 (0%) 0
    Erythema 1/4 (25%) 1 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/9 (11.1%) 1 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 1/21 (4.8%) 4
    Macule 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 0/21 (0%) 0
    Night sweats 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/9 (11.1%) 1 0/6 (0%) 0 1/4 (25%) 1 3/42 (7.1%) 3 0/21 (0%) 0
    Pain of skin 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 1/21 (4.8%) 1
    Palmar-plantar erythrodysaesthesia syndrome 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 0/21 (0%) 0
    Papule 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 2/42 (4.8%) 2 0/21 (0%) 0
    Perioral dermatitis 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 0/21 (0%) 0
    Pruritus 0/4 (0%) 0 0/5 (0%) 0 1/3 (33.3%) 2 1/3 (33.3%) 1 5/9 (55.6%) 10 0/6 (0%) 0 0/4 (0%) 0 7/42 (16.7%) 10 3/21 (14.3%) 4
    Rash 2/4 (50%) 2 1/5 (20%) 1 0/3 (0%) 0 1/3 (33.3%) 1 4/9 (44.4%) 4 2/6 (33.3%) 2 0/4 (0%) 0 7/42 (16.7%) 9 4/21 (19%) 4
    Rash maculo-papular 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 2/42 (4.8%) 5 4/21 (19%) 5
    Rash papular 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 1/21 (4.8%) 1
    Rash pruritic 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 1/21 (4.8%) 1
    Scar pain 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 1/4 (25%) 1 0/42 (0%) 0 0/21 (0%) 0
    Skin discolouration 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/9 (11.1%) 1 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 0/21 (0%) 0
    Skin fissures 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 0/21 (0%) 0
    Skin lesion 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 1/6 (16.7%) 1 1/4 (25%) 2 1/42 (2.4%) 1 1/21 (4.8%) 1
    Skin ulcer 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 1/21 (4.8%) 1
    Urticaria 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/9 (11.1%) 1 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 0/21 (0%) 0
    Vitiligo 1/4 (25%) 1 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 0/42 (0%) 0 0/21 (0%) 0
    Xeroderma 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 1/6 (16.7%) 1 0/4 (0%) 0 0/42 (0%) 0 0/21 (0%) 0
    Vascular disorders
    Aortic aneurysm 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 0/21 (0%) 0
    Aortic occlusion 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 0/21 (0%) 0
    Deep vein thrombosis 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 1/21 (4.8%) 1
    Embolism 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 1/6 (16.7%) 1 0/4 (0%) 0 0/42 (0%) 0 0/21 (0%) 0
    Flushing 1/4 (25%) 2 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/9 (11.1%) 1 1/6 (16.7%) 1 0/4 (0%) 0 1/42 (2.4%) 1 0/21 (0%) 0
    Hot flush 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 1/21 (4.8%) 1
    Hypertension 1/4 (25%) 1 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/9 (11.1%) 1 1/6 (16.7%) 3 1/4 (25%) 1 5/42 (11.9%) 7 0/21 (0%) 0
    Hypotension 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 1/4 (25%) 1 2/42 (4.8%) 2 1/21 (4.8%) 1
    Vena cava embolism 0/4 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/9 (0%) 0 0/6 (0%) 0 0/4 (0%) 0 1/42 (2.4%) 1 0/21 (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 on going 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 Farzana Walcott
    Organization MedImmune, LLC
    Phone +1 301-398-3063
    Email information.center@astrazeneca.com
    Responsible Party:
    MedImmune LLC
    ClinicalTrials.gov Identifier:
    NCT02118337
    Other Study ID Numbers:
    • D6020C00001
    First Posted:
    Apr 21, 2014
    Last Update Posted:
    Jun 1, 2021
    Last Verified:
    May 1, 2021