A Phase 1 Study to Evaluate MEDI4736 in Combination With Tremelimumab

Sponsor

Ludwig Institute for Cancer Research (Other)

Overall Status

Completed

CT.gov ID

NCT01975831

Collaborator

MedImmune LLC (Industry), Cancer Research Institute, New York City (Other)

104

Enrollment

Locations

Arms

90.4

Actual Duration (Months)

17.3

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This was a Phase 1, open-label, nonrandomized, multicenter study of durvalumab and tremelimumab in subjects with advanced cancers who were not eligible for, declined, or failed standard treatment. The primary study objective was to determine the maximum tolerated dose (MTD) and safety profile of the durvalumab and tremelimumab combination. Secondary objectives were to evaluate the pharmacokinetics (PK) and immunogenicity of durvalumab and tremelimumab, and the antitumor activity (tumor response, progression-free survival [PFS], and overall survival [OS]) of the durvalumab and tremelimumab combination. (Note: Collection of PK and immunogenicity samples was removed by amendment; analysis was not done.) Exploratory objectives were to evaluate the biological activity of the durvalumab and tremelimumab combination.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer Ovarian Cancer Colorectal Cancer Cervical Cancer Renal Cell Carcinoma	Drug: Durvalumab Drug: Tremelimumab	Phase 1

Detailed Description

The study comprised a 3 + 3 dose escalation phase in which 3 to 6 subjects were enrolled into sequential cohorts until determination of the MTD, followed by an expansion phase in 5 tumor type-specific cohorts (i.e., ovarian cancer, colorectal cancer, non-triple negative breast cancer, renal cell carcinoma, and cervical cancer). Each expansion cohort was to include 15 subjects treated with the identified MTD or maximum dose tested in the dose-escalation phase.

Subjects received durvalumab and tremelimumab over 12 to 13 four-week cycles during the Core Study, with continuous monitoring for safety, clinical efficacy, and biological activity, followed by optional treatment extension with durvalumab for subjects maintaining at least stable disease if agreed upon by the Investigator and Sponsor. After study treatment completion, study assessments were continued for up to 90 days after the last administration of study treatment or until start of alternate therapy, with long-term follow up after study completion for clinical outcomes at least every 6 months for up to 3 years following initiation of treatment.

Study treatment in the Core Study continued for up to 12 months or until confirmed progressive disease (PD), initiation of alternative cancer therapy, observation of unacceptable toxicity, or any other criteria for treatment discontinuation.

Optional treatment extension beyond the Core Study was permitted for subjects who completed the Core Study with a tumor response of stable disease or better and upon agreement by the Sponsor and Investigator. Extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg administered every 4 weeks (Q4W).

Study Design

Study Type:

Interventional

Actual Enrollment :

104 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 1 Study to Evaluate the Safety and Tolerability of Anti-PD-L1, MEDI4736, in Combination With Tremelimumab in Subjects With Advanced Solid Tumors

Actual Study Start Date :

Dec 19, 2013

Actual Primary Completion Date :

Dec 1, 2019

Actual Study Completion Date :

Jul 2, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Escalation: 0.3 mg/kg Durva + 3 mg/kg Treme Subjects received durvalumab (0.3 mg/kg every 2 weeks [Q2W] for 13 cycles) and tremelimumab (3 mg/kg every 4 weeks [Q4W] for 6 cycles, then every 12 weeks [Q12W]). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W.	Drug: Durvalumab Durvalumab was administered as an intravenous (IV) infusion over 60 (± 5) minutes. Other Names: MEDI4736 Durva Drug: Tremelimumab Tremelimumab was administered as an intravenous (IV) infusion over 60 (± 5) minutes. Other Names: Treme
Experimental: Escalation: 1 mg/kg Durva + 3 mg/kg Treme Subjects received durvalumab (1 mg/kg Q2W for 13 cycles) and tremelimumab (3 mg/kg Q4W for 6 cycles, then Q12W). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W.	Drug: Durvalumab Durvalumab was administered as an intravenous (IV) infusion over 60 (± 5) minutes. Other Names: MEDI4736 Durva Drug: Tremelimumab Tremelimumab was administered as an intravenous (IV) infusion over 60 (± 5) minutes. Other Names: Treme
Experimental: Escalation: 3 mg/kg Durva + 3 mg/kg Treme Subjects received durvalumab (3 mg/kg Q2W for 13 cycles) and tremelimumab (3 mg/kg Q4W for 6 cycles, then Q12W). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W.	Drug: Durvalumab Durvalumab was administered as an intravenous (IV) infusion over 60 (± 5) minutes. Other Names: MEDI4736 Durva Drug: Tremelimumab Tremelimumab was administered as an intravenous (IV) infusion over 60 (± 5) minutes. Other Names: Treme
Experimental: Escalation: 3 mg/kg Durva + 1 mg/kg Treme Subjects received durvalumab (3 mg/kg Q2W for 12 or 13 cycles) and tremelimumab (1 mg/kg Q4W for 6 cycles, then Q12W or Q4W for 4 cycles). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W.	Drug: Durvalumab Durvalumab was administered as an intravenous (IV) infusion over 60 (± 5) minutes. Other Names: MEDI4736 Durva Drug: Tremelimumab Tremelimumab was administered as an intravenous (IV) infusion over 60 (± 5) minutes. Other Names: Treme
Experimental: Expansion: Ovarian Cancer Subjects received durvalumab (10 mg/kg Q2W for 13 cycles or 1500 mg Q4W for 12 cycles) and tremelimumab (1 mg/kg or 75 mg Q4W for 4 cycles). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W.	Drug: Durvalumab Durvalumab was administered as an intravenous (IV) infusion over 60 (± 5) minutes. Other Names: MEDI4736 Durva Drug: Tremelimumab Tremelimumab was administered as an intravenous (IV) infusion over 60 (± 5) minutes. Other Names: Treme
Experimental: Expansion: Colorectal Cancer Subjects received durvalumab (10 mg/kg Q2W for 13 cycles or 1500 mg Q4W for 12 cycles) and tremelimumab (1 mg/kg or 75 mg Q4W for 4 cycles). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W.	Drug: Durvalumab Durvalumab was administered as an intravenous (IV) infusion over 60 (± 5) minutes. Other Names: MEDI4736 Durva Drug: Tremelimumab Tremelimumab was administered as an intravenous (IV) infusion over 60 (± 5) minutes. Other Names: Treme
Experimental: Expansion: Non-triple Negative Breast Cancer Subjects received durvalumab (10 mg/kg Q2W for 13 cycles or 1500 mg Q4W for 12 cycles) and tremelimumab (1 mg/kg or 75 mg Q4W for 4 cycles). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W.	Drug: Durvalumab Durvalumab was administered as an intravenous (IV) infusion over 60 (± 5) minutes. Other Names: MEDI4736 Durva Drug: Tremelimumab Tremelimumab was administered as an intravenous (IV) infusion over 60 (± 5) minutes. Other Names: Treme
Experimental: Expansion: Renal Cell Carcinoma Subjects received durvalumab (10 mg/kg Q2W for 13 cycles or 1500 mg Q4W for 12 cycles) and tremelimumab (1 mg/kg or 75 mg Q4W for 4 cycles). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W.	Drug: Durvalumab Durvalumab was administered as an intravenous (IV) infusion over 60 (± 5) minutes. Other Names: MEDI4736 Durva Drug: Tremelimumab Tremelimumab was administered as an intravenous (IV) infusion over 60 (± 5) minutes. Other Names: Treme
Experimental: Expansion: Cervical Cancer Subjects received durvalumab (10 mg/kg Q2W for 13 cycles or 1500 mg Q4W for 12 cycles) and tremelimumab (1 mg/kg or 75 mg Q4W for 4 cycles). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W.	Drug: Durvalumab Durvalumab was administered as an intravenous (IV) infusion over 60 (± 5) minutes. Other Names: MEDI4736 Durva Drug: Tremelimumab Tremelimumab was administered as an intravenous (IV) infusion over 60 (± 5) minutes. Other Names: Treme

Outcome Measures

Primary Outcome Measures

Number of Subjects With Treatment-emergent Adverse Events (TEAEs) [Up to 36 months]
Toxicity was graded in accordance with the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 4.03. Adverse events (AEs) were reported based on clinical laboratory tests, vital sign and weight measurements, physical examinations, performance status evaluations, electrocardiograms, magnetic resonance imaging, and any other medically indicated assessments, including subject interviews, from the time informed consent is signed through 90 days after the last dose of study treatment. AEs were considered to be treatment emergent (TEAE) if they occurred or worsened in severity after the first dose of study treatment.

Secondary Outcome Measures

Number of Subjects With Best Overall Immune-related Tumor Response [Up to 24 months]
Immune-related tumor response was evaluated by computed tomography at Baseline and every 4 to 8 or 12 weeks on study. Tumor response was designated according to the immune-related Response Criteria (irRC) (Wolchok et al 2009) into the following categories: immune-related complete response (irCR) requires disappearance of all lesions in two consecutive observations not less than 4 weeks apart; immune-related partial response (irPR) requires ≥ 50% decrease in tumor burden compared with baseline in two observations at least 4 weeks apart; immune-related stable disease (irSD) is assigned when neither a 50% decrease from baseline tumor burden nor a 25% increase in tumor burden from nadir can be established; immune-related progressive disease (irPD) requires a ≥ 25% increase from nadir in tumor burden at any single time point in two consecutive observations at least 4 weeks apart.
Number of Subjects With Best Overall Tumor Response by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 [Up to 24 months]
Tumor response was evaluated using computed tomography and categorized according to RECIST (version 1.1) at Baseline and every 4 to 8 or 12 weeks on study. Per RECIST 1.1 (Eisenhauer et al 2009), target lesions are categorized as follows: Complete Response (CR): Disappearance of all target lesions; Partial Response (PR): ≥ 30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD): ≥ 20% increase in the sum of the longest diameter of target lesions; Stable Disease (SD): small changes that do not meet above criteria.
Median Progression-free Survival Per irRC Based on Kaplan-Meier Product Limit Estimates [Up to 36 months]
PFS was measured from the date of the first dose of study treatment to the date of the first confirmed progression (including clinical progression) or the date of death if a subject died before progression. Per irRC, irPD requires a ≥ 25% increase from nadir in tumor burden at any single time point in two consecutive observations at least 4 weeks apart (Wolchok et al 2009). Subjects who did not experience a PFS event (progression or death) were censored at the date of the last tumor assessment. Subjects with no relevant tumor response assessment were censored at the start date of study treatment.
Median Progression-free Survival Per RECIST 1.1 Based on Kaplan-Meier Product Limit Estimates [Up to 36 months]
PFS was measured from the date of the first dose of study treatment to the date of the first confirmed progression (including clinical progression) or the date of death if a subject died before progression. Per RECIST 1.1, PD requires a ≥ 20% increase in the sum of the longest diameter of target lesions (Eisenhauer et al 2009). Subjects who did not experience a PFS event (progression or death) were censored at the date of the last tumor assessment. Subjects with no relevant tumor response assessment were censored at the start date of study treatment.
Median Overall Survival (OS) Based on Kaplan-Meier Product Limit Estimates [Up to 48 months]
All subjects were monitored for survival follow-up at least every 6 months after study completion for up to 3 years after initiation of treatment. Subjects who continued into the Extension part of the study may have been followed for longer than 3 years if they were still receiving treatment. OS was measured from the date of the first dose of study treatment until the recorded date of death. Subjects without a recorded outcome of death were censored at the date of last contact.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria

Histologically- or cytologically-confirmed ovarian cancer, colorectal cancer, non-triple negative breast cancer, renal cell carcinoma and cervical cancer, with at least one lesion measurable by the immune-related Response Criteria (irRC) not previously irradiated. NOTE: Per Amendment 5, the disease states of non-small cell lung cancer and head and neck cancer were removed from the study and were replaced by non-triple negative breast cancer.
Failed to respond to or relapsed following standard treatment or declined or was not eligible for standard treatment.
Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2.
Anticipated lifespan greater than 6 months.
At the time of Day 1 of the study, subjects with brain metastases must have been asymptomatic for at least 4 weeks and:

at least 8 weeks without tumor progression after any whole brain radiotherapy;
at least 4 weeks since craniotomy and resection or stereotactic radiosurgery;
at least 3 weeks without new brain metastases as evidenced by magnetic resonance imaging (MRI)/computed tomography (CT).

Adequate organ and marrow function, as defined below:

hemoglobin ≥ 9 g/dL
absolute neutrophil count ≥ 1500/mm^3
platelet count ≥ 100,000/mm^3
total bilirubin within normal ranges unless associated with hepatobiliary metastases or Gilbert syndrome, then total bilirubin ≤ 2 × the upper limit of normal (ULN)
alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN unless associated with hepatic metastases, then ALT and AST ≤ 5 × ULN
creatinine ≤ 2.0 mg/dL

Have been informed of other treatment options.
Age ≥ 18 years.
Able and willing to give valid written informed consent.
Able and willing to give valid written consent for archival tumor samples.
Able and willing to give valid written consent for biopsy samples (subjects with biopsiable tumors, and if clinically appropriate, in the expansion phase only).

Exclusion Criteria

Prior exposure to tremelimumab or durvalumab or other anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), anti-programmed cell death-1 (PD-1), anti-programmed cell death ligand-1 (PD-L1) antibodies.
History of severe allergic reactions to any unknown allergens or any components of the study drugs.
Active or prior autoimmune disease except for autoimmune thyroiditis or vitiligo.
Any prior Grade ≥ 3 immune-related adverse event (irAE) or any prior corticosteroid-refractory irAE.
Known active or chronic viral hepatitis or history of any type of hepatitis within the last 6 months.
History of sarcoidosis syndrome.
Active or history of inflammatory bowel disease (colitis, Crohn's), diverticulitis, irritable bowel disease, celiac disease, or other serious, chronic, gastrointestinal conditions associated with diarrhea. Active or history of systemic lupus erythematosus or Wegener's granulomatosis.
Metastatic disease to the central nervous system for which other therapeutic options, including radiotherapy, may have been available.
Known immunodeficiency or active human immunodeficiency virus (HIV).
Other active serious illnesses (e.g., serious infections requiring antibiotics).
If a subject previously received investigational treatment, the last dose of investigational treatment was administered within 4 weeks of Day 1 of the study or AE(s) attributable to investigational treatment had not resolved to Grade 1 or better.
Major surgical procedure (as defined by the Investigator) within 30 days prior to Day 1 or still recovering from prior surgery.
Mental impairment that may have compromised the ability to give informed consent and comply with the requirements of the study.
Lack of availability for immunological and clinical follow-up assessments.
Women who were breast feeding or pregnant as evidenced by positive serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin [HCG]).
Female subjects of childbearing potential who were sexually active with a non-sterilized male partner must have used at least one highly effective method of contraception from the time of screening and must have agreed to continue using such precautions for 90 days after the last dose of durvalumab or for 6 months after the final dose of durvalumab + tremelimumab (whichever was longer). Non-sterilized male partners of a female subject must have used male condoms plus spermicide throughout this period. Cessation of birth control after this point should have been discussed with a responsible physician. Not engaging in sexual activity for the total duration of the trial and the drug washout period was an acceptable practice; however, periodic abstinence, the rhythm method, and the withdrawal method were not acceptable methods of birth control.

Female subjects should have also refrained from breastfeeding throughout the period described above.

Females of childbearing potential were defined as those who were not surgically sterile (i.e., bilateral tubal ligation, bilateral oophorectomy, or complete hysterectomy) or post-menopausal.

Females were considered post-menopausal if they had been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements applied:

Females <50 years of age were considered post-menopausal if they had been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they had luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy).
Females ≥ 50 years of age were considered post-menopausal if they had been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses >1 year ago, had chemotherapy-induced menopause with last menses >1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy).

Non-sterilized male subjects who were sexually active with a female partner of childbearing potential must have used male condoms plus spermicide from screening through 90 days after the last dose of durvalumab or through 6 months after receipt of the final dose of durvalumab + tremelimumab (whichever was longer). Female partners (of childbearing potential) of a male subject must have used a highly effective method of contraception throughout this period. Cessation of birth control after this point should have been discussed with a responsible physician. Not engaging in sexual activity for the total duration of the trial and the drug washout period was an acceptable practice; however, periodic abstinence, the rhythm method, and the withdrawal method were not acceptable methods of contraception.

Male subjects should have refrained from sperm donation throughout the period described above.

A highly effective method of contraception was defined as one that resulted in a low failure rate (i.e. less than 1% per year) when used consistently and correctly. Note that some contraception methods were not considered highly effective (e.g., male or female condom with or without spermicide; female cap, diaphragm, or sponge with or without spermicide; non-copper containing intrauterine device; progestogen-only oral hormonal contraceptive pills where inhibition of ovulation is not the primary mode of action [excluding Cerazette/desogestrel which was considered highly effective]; and triphasic combined oral contraceptive pills).

Any condition that, in the clinical judgment of the treating physician, was likely to prevent the subject from complying with any aspect of the protocol or that may have put the subject at unacceptable risk.
Subjects must not have donated blood while on study and for at least 90 days following the last durvalumab treatment or 6 months after the last tremelimumab treatment, whichever was longer.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Yale Cancer Center	New Haven	Connecticut	United States	06510
2	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02215
3	Roswell Park Cancer Institute	Buffalo	New York	United States	14203
4	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
5	Mary Crowley Cancer Research Center	Dallas	Texas	United States	75230
6	University of Virginia Division of Hematology and Oncology	Charlottesville	Virginia	United States	22903

Sponsors and Collaborators

Ludwig Institute for Cancer Research
MedImmune LLC
Cancer Research Institute, New York City

Investigators

Study Chair: Jedd D Wolchok, MD, PhD, Memorial Sloan Kettering Cancer Center

Study Documents (Full-Text)

Study Protocol and Statistical Analysis Plan - Jan 8, 2019

More Information

Publications

Responsible Party:

Ludwig Institute for Cancer Research

ClinicalTrials.gov Identifier:

NCT01975831

Other Study ID Numbers:

LUD2013-003

First Posted:

Nov 5, 2013

Last Update Posted:

Jul 15, 2021

Last Verified:

Jul 1, 2021

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Carcinoma, Renal Cell

Durvalumab

Tremelimumab

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail

Arm/Group Title	Escalation: 0.3 mg/kg Durva + 3 mg/kg Treme	Escalation: 1 mg/kg Durva + 3 mg/kg Treme	Escalation: 3 mg/kg Durva + 3 mg/kg Treme	Escalation: 3 mg/kg Durva + 1 mg/kg Treme	Expansion: Ovarian Cancer	Expansion: Colorectal Cancer	Expansion: Non-triple Negative Breast Cancer	Expansion: Renal Cell Carcinoma	Expansion: Cervical Cancer
Arm/Group Description	Subjects received durvalumab (0.3 mg/kg every 2 weeks [Q2W] for 13 cycles) and tremelimumab (3 mg/kg every 4 weeks [Q4W] for 6 cycles, then every 12 weeks [Q12W]). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W. Durvalumab and tremelimumab were administered as intravenous (IV) infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.	Subjects received durvalumab (1 mg/kg Q2W for 13 cycles) and tremelimumab (3 mg/kg Q4W for 6 cycles, then Q12W). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W. Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.	Subjects received durvalumab (3 mg/kg Q2W for 13 cycles) and tremelimumab (3 mg/kg Q4W for 6 cycles, then Q12W). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W. Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.	Subjects received durvalumab (3 mg/kg Q2W for 12 or 13 cycles) and tremelimumab (1 mg/kg Q4W for 6 cycles, then Q12W or Q4W for 4 cycles). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W. Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.	Subjects received durvalumab (10 mg/kg Q2W for 13 cycles or 1500 mg Q4W for 12 cycles) and tremelimumab (1 mg/kg or 75 mg Q4W for 4 cycles). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W. Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.	Subjects received durvalumab (10 mg/kg Q2W for 13 cycles or 1500 mg Q4W for 12 cycles) and tremelimumab (1 mg/kg or 75 mg Q4W for 4 cycles). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W. Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.	Subjects received durvalumab (10 mg/kg Q2W for 13 cycles or 1500 mg Q4W for 12 cycles) and tremelimumab (1 mg/kg or 75 mg Q4W for 4 cycles). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W. Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.	Subjects received durvalumab (10 mg/kg Q2W for 13 cycles or 1500 mg Q4W for 12 cycles) and tremelimumab (1 mg/kg or 75 mg Q4W for 4 cycles). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W. Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.	Subjects received durvalumab (10 mg/kg Q2W for 13 cycles or 1500 mg Q4W for 12 cycles) and tremelimumab (1 mg/kg or 75 mg Q4W for 4 cycles). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W. Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.
Period Title: Overall Study
STARTED	3	11	4	4	19	16	16	16	15
COMPLETED	0	2	0	0	1	2	0	1	3
NOT COMPLETED	3	9	4	4	18	14	16	15	12

Baseline Characteristics

Arm/Group Title	Escalation: 0.3 mg/kg Durva + 3 mg/kg Treme	Escalation: 1 mg/kg Durva + 3 mg/kg Treme	Escalation: 3 mg/kg Durva + 3 mg/kg Treme	Escalation: 3 mg/kg Durva + 1 mg/kg Treme	Expansion: Ovarian Cancer	Expansion: Colorectal Cancer	Expansion: Non-triple Negative Breast Cancer	Expansion: Renal Cell Carcinoma	Expansion: Cervical Cancer	Total
Arm/Group Description	Subjects received durvalumab (0.3 mg/kg Q2W for 13 cycles) and tremelimumab (3 mg/kg Q4W for 6 cycles, then Q12W). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W. Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.	Subjects received durvalumab (1 mg/kg Q2W for 13 cycles) and tremelimumab (3 mg/kg Q4W for 6 cycles, then Q12W). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W. Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.	Subjects received durvalumab (3 mg/kg Q2W for 13 cycles) and tremelimumab (3 mg/kg Q4W for 6 cycles, then Q12W). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W. Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.	Subjects received durvalumab (3 mg/kg Q2W for 12 or 13 cycles) and tremelimumab (1 mg/kg Q4W for 6 cycles, then Q12W or Q4W for 4 cycles). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W. Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.	Subjects received durvalumab (10 mg/kg Q2W for 13 cycles or 1500 mg Q4W for 12 cycles) and tremelimumab (1 mg/kg or 75 mg Q4W for 4 cycles). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W. Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.	Subjects received durvalumab (10 mg/kg Q2W for 13 cycles or 1500 mg Q4W for 12 cycles) and tremelimumab (1 mg/kg or 75 mg Q4W for 4 cycles). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W. Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.	Subjects received durvalumab (10 mg/kg Q2W for 13 cycles or 1500 mg Q4W for 12 cycles) and tremelimumab (1 mg/kg or 75 mg Q4W for 4 cycles). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W. Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.	Subjects received durvalumab (10 mg/kg Q2W for 13 cycles or 1500 mg Q4W for 12 cycles) and tremelimumab (1 mg/kg or 75 mg Q4W for 4 cycles). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W. Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.	Subjects received durvalumab (10 mg/kg Q2W for 13 cycles or 1500 mg Q4W for 12 cycles) and tremelimumab (1 mg/kg or 75 mg Q4W for 4 cycles). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W. Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.	Total of all reporting groups
Overall Participants	3	11	4	4	19	16	16	16	15	104
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	61.3 (7.51)	54.9 (11.93)	50.3 (10.21)	52.8 (11.35)	59.7 (10.91)	49.7 (9.79)	55.4 (14.31)	59.7 (9.71)	53.0 (11.46)	55.5 (11.51)
Sex: Female, Male (Count of Participants)
Female	3 100%	6 54.5%	3 75%	3 75%	19 100%	9 56.3%	16 100%	2 12.5%	15 100%	76 73.1%
Male	0 0%	5 45.5%	1 25%	1 25%	0 0%	7 43.8%	0 0%	14 87.5%	0 0%	28 26.9%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	1 9.1%	1 25%	0 0%	1 5.3%	1 6.3%	1 6.3%	0 0%	0 0%	5 4.8%
Not Hispanic or Latino	3 100%	10 90.9%	3 75%	4 100%	17 89.5%	14 87.5%	14 87.5%	16 100%	12 80%	93 89.4%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	1 5.3%	1 6.3%	1 6.3%	0 0%	3 20%	6 5.8%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	1 25%	0 0%	1 5.3%	2 12.5%	0 0%	1 6.3%	3 20%	8 7.7%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	1 5.3%	0 0%	0 0%	0 0%	0 0%	1 1%
Black or African American	0 0%	0 0%	0 0%	0 0%	1 5.3%	0 0%	2 12.5%	0 0%	2 13.3%	5 4.8%
White	3 100%	10 90.9%	2 50%	4 100%	16 84.2%	12 75%	12 75%	15 93.8%	9 60%	83 79.8%
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%	1 9.1%	1 25%	0 0%	0 0%	2 12.5%	2 12.5%	0 0%	1 6.7%	7 6.7%
Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) (Count of Participants)
ECOG PS 0	2 66.7%	2 18.2%	2 50%	1 25%	7 36.8%	9 56.3%	6 37.5%	14 87.5%	9 60%	52 50%
ECOG PS 1	1 33.3%	9 81.8%	2 50%	2 50%	11 57.9%	7 43.8%	10 62.5%	2 12.5%	6 40%	50 48.1%
ECOG PS 2	0 0%	0 0%	0 0%	1 25%	1 5.3%	0 0%	0 0%	0 0%	0 0%	2 1.9%

Outcome Measures

1. Primary Outcome

Title	Number of Subjects With Treatment-emergent Adverse Events (TEAEs)
Description	Toxicity was graded in accordance with the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 4.03. Adverse events (AEs) were reported based on clinical laboratory tests, vital sign and weight measurements, physical examinations, performance status evaluations, electrocardiograms, magnetic resonance imaging, and any other medically indicated assessments, including subject interviews, from the time informed consent is signed through 90 days after the last dose of study treatment. AEs were considered to be treatment emergent (TEAE) if they occurred or worsened in severity after the first dose of study treatment.
Time Frame	Up to 36 months

Outcome Measure Data

Analysis Population Description
The population comprises all subjects who received any dose of study treatment.

Arm/Group Title	Escalation: 0.3 mg/kg Durva + 3 mg/kg Treme	Escalation: 1 mg/kg Durva + 3 mg/kg Treme	Escalation: 3 mg/kg Durva + 3 mg/kg Treme	Escalation: 3 mg/kg Durva + 1 mg/kg Treme	Expansion: Ovarian Cancer	Expansion: Colorectal Cancer	Expansion: Non-triple Negative Breast Cancer	Expansion: Renal Cell Carcinoma	Expansion: Cervical Cancer
Arm/Group Description	Subjects received durvalumab (0.3 mg/kg Q2W for 13 cycles) and tremelimumab (3 mg/kg Q4W for 6 cycles, then Q12W). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W. Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.	Subjects received durvalumab (1 mg/kg Q2W for 13 cycles) and tremelimumab (3 mg/kg Q4W for 6 cycles, then Q12W). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W. Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.	Subjects received durvalumab (3 mg/kg Q2W for 13 cycles) and tremelimumab (3 mg/kg Q4W for 6 cycles, then Q12W). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W. Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.	Subjects received durvalumab (3 mg/kg Q2W for 12 or 13 cycles) and tremelimumab (1 mg/kg Q4W for 6 cycles, then Q12W or Q4W for 4 cycles). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W. Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.	Subjects received durvalumab (10 mg/kg Q2W for 13 cycles or 1500 mg Q4W for 12 cycles) and tremelimumab (1 mg/kg or 75 mg Q4W for 4 cycles). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W. Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.	Subjects received durvalumab (10 mg/kg Q2W for 13 cycles or 1500 mg Q4W for 12 cycles) and tremelimumab (1 mg/kg or 75 mg Q4W for 4 cycles). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W. Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.	Subjects received durvalumab (10 mg/kg Q2W for 13 cycles or 1500 mg Q4W for 12 cycles) and tremelimumab (1 mg/kg or 75 mg Q4W for 4 cycles). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W. Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.	Subjects received durvalumab (10 mg/kg Q2W for 13 cycles or 1500 mg Q4W for 12 cycles) and tremelimumab (1 mg/kg or 75 mg Q4W for 4 cycles). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W. Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.	Subjects received durvalumab (10 mg/kg Q2W for 13 cycles or 1500 mg Q4W for 12 cycles) and tremelimumab (1 mg/kg or 75 mg Q4W for 4 cycles). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W. Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.
Measure Participants	3	11	4	4	19	16	16	16	15
Any TEAE	3 100%	11 100%	4 100%	4 100%	19 100%	16 100%	16 100%	16 100%	15 100%
Serious TEAE	2 66.7%	5 45.5%	4 100%	1 25%	9 47.4%	8 50%	8 50%	6 37.5%	8 53.3%
TEAE leading to treatment discontinuation	1 33.3%	4 36.4%	2 50%	0 0%	4 21.1%	1 6.3%	4 25%	4 25%	2 13.3%

2. Secondary Outcome

Title	Number of Subjects With Best Overall Immune-related Tumor Response
Description	Immune-related tumor response was evaluated by computed tomography at Baseline and every 4 to 8 or 12 weeks on study. Tumor response was designated according to the immune-related Response Criteria (irRC) (Wolchok et al 2009) into the following categories: immune-related complete response (irCR) requires disappearance of all lesions in two consecutive observations not less than 4 weeks apart; immune-related partial response (irPR) requires ≥ 50% decrease in tumor burden compared with baseline in two observations at least 4 weeks apart; immune-related stable disease (irSD) is assigned when neither a 50% decrease from baseline tumor burden nor a 25% increase in tumor burden from nadir can be established; immune-related progressive disease (irPD) requires a ≥ 25% increase from nadir in tumor burden at any single time point in two consecutive observations at least 4 weeks apart.
Time Frame	Up to 24 months

Outcome Measure Data

Analysis Population Description
The population comprises all subjects who received at least one dose of the durvalumab/tremelimumab combination and had the baseline and at least one post-baseline assessment of any efficacy endpoint (clinical or radiological) or a report of death.

Arm/Group Title	Escalation: 0.3 mg/kg Durva + 3 mg/kg Treme	Escalation: 1 mg/kg Durva + 3 mg/kg Treme	Escalation: 3 mg/kg Durva + 3 mg/kg Treme	Escalation: 3 mg/kg Durva + 1 mg/kg Treme	Expansion: Ovarian Cancer	Expansion: Colorectal Cancer	Expansion: Non-triple Negative Breast Cancer	Expansion: Renal Cell Carcinoma	Expansion: Cervical Cancer
Arm/Group Description	Subjects received durvalumab (0.3 mg/kg Q2W for 13 cycles) and tremelimumab (3 mg/kg Q4W for 6 cycles, then Q12W). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W. Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.	Subjects received durvalumab (1 mg/kg Q2W for 13 cycles) and tremelimumab (3 mg/kg Q4W for 6 cycles, then Q12W). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W. Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.	Subjects received durvalumab (3 mg/kg Q2W for 13 cycles) and tremelimumab (3 mg/kg Q4W for 6 cycles, then Q12W). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W. Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.	Subjects received durvalumab (3 mg/kg Q2W for 12 or 13 cycles) and tremelimumab (1 mg/kg Q4W for 6 cycles, then Q12W or Q4W for 4 cycles). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W. Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.	Subjects received durvalumab (10 mg/kg Q2W for 13 cycles or 1500 mg Q4W for 12 cycles) and tremelimumab (1 mg/kg or 75 mg Q4W for 4 cycles). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W. Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.	Subjects received durvalumab (10 mg/kg Q2W for 13 cycles or 1500 mg Q4W for 12 cycles) and tremelimumab (1 mg/kg or 75 mg Q4W for 4 cycles). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W. Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.	Subjects received durvalumab (10 mg/kg Q2W for 13 cycles or 1500 mg Q4W for 12 cycles) and tremelimumab (1 mg/kg or 75 mg Q4W for 4 cycles). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W. Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.	Subjects received durvalumab (10 mg/kg Q2W for 13 cycles or 1500 mg Q4W for 12 cycles) and tremelimumab (1 mg/kg or 75 mg Q4W for 4 cycles). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W. Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.	Subjects received durvalumab (10 mg/kg Q2W for 13 cycles or 1500 mg Q4W for 12 cycles) and tremelimumab (1 mg/kg or 75 mg Q4W for 4 cycles). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W. Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.
Measure Participants	3	10	3	4	18	15	16	15	15
irCR	0 0%	0 0%	0 0%	0 0%	0 0%	1 6.3%	0 0%	0 0%	1 6.7%
irPR	0 0%	2 18.2%	0 0%	0 0%	1 5.3%	1 6.3%	1 6.3%	2 12.5%	3 20%
irSD	2 66.7%	3 27.3%	1 25%	0 0%	7 36.8%	1 6.3%	2 12.5%	11 68.8%	3 20%
irPD	1 33.3%	5 45.5%	2 50%	4 100%	10 52.6%	12 75%	12 75%	2 12.5%	7 46.7%
Not evaluable	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 6.3%	0 0%	1 6.7%

3. Secondary Outcome

Title	Number of Subjects With Best Overall Tumor Response by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
Description	Tumor response was evaluated using computed tomography and categorized according to RECIST (version 1.1) at Baseline and every 4 to 8 or 12 weeks on study. Per RECIST 1.1 (Eisenhauer et al 2009), target lesions are categorized as follows: Complete Response (CR): Disappearance of all target lesions; Partial Response (PR): ≥ 30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD): ≥ 20% increase in the sum of the longest diameter of target lesions; Stable Disease (SD): small changes that do not meet above criteria.
Time Frame	Up to 24 months

Outcome Measure Data

Analysis Population Description
The population comprises all subjects who received at least one dose of the durvalumab/tremelimumab combination and had the baseline and at least one post-baseline assessment of any efficacy endpoint (clinical or radiological) or a report of death.

Arm/Group Title	Escalation: 0.3 mg/kg Durva + 3 mg/kg Treme	Escalation: 1 mg/kg Durva + 3 mg/kg Treme	Escalation: 3 mg/kg Durva + 3 mg/kg Treme	Escalation: 3 mg/kg Durva + 1 mg/kg Treme	Expansion: Ovarian Cancer	Expansion: Colorectal Cancer	Expansion: Non-triple Negative Breast Cancer	Expansion: Renal Cell Carcinoma	Expansion: Cervical Cancer
Arm/Group Description	Subjects received durvalumab (0.3 mg/kg Q2W for 13 cycles) and tremelimumab (3 mg/kg Q4W for 6 cycles, then Q12W). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W. Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.	Subjects received durvalumab (1 mg/kg Q2W for 13 cycles) and tremelimumab (3 mg/kg Q4W for 6 cycles, then Q12W). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W. Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.	Subjects received durvalumab (3 mg/kg Q2W for 13 cycles) and tremelimumab (3 mg/kg Q4W for 6 cycles, then Q12W). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W. Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.	Subjects received durvalumab (3 mg/kg Q2W for 12 or 13 cycles) and tremelimumab (1 mg/kg Q4W for 6 cycles, then Q12W or Q4W for 4 cycles). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W. Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.	Subjects received durvalumab (10 mg/kg Q2W for 13 cycles or 1500 mg Q4W for 12 cycles) and tremelimumab (1 mg/kg or 75 mg Q4W for 4 cycles). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W. Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.	Subjects received durvalumab (10 mg/kg Q2W for 13 cycles or 1500 mg Q4W for 12 cycles) and tremelimumab (1 mg/kg or 75 mg Q4W for 4 cycles). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W. Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.	Subjects received durvalumab (10 mg/kg Q2W for 13 cycles or 1500 mg Q4W for 12 cycles) and tremelimumab (1 mg/kg or 75 mg Q4W for 4 cycles). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W. Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.	Subjects received durvalumab (10 mg/kg Q2W for 13 cycles or 1500 mg Q4W for 12 cycles) and tremelimumab (1 mg/kg or 75 mg Q4W for 4 cycles). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W. Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.	Subjects received durvalumab (10 mg/kg Q2W for 13 cycles or 1500 mg Q4W for 12 cycles) and tremelimumab (1 mg/kg or 75 mg Q4W for 4 cycles). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W. Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.
Measure Participants	3	10	3	4	18	15	16	15	15
CR	0 0%	0 0%	0 0%	0 0%	0 0%	1 6.3%	0 0%	0 0%	1 6.7%
PR	0 0%	2 18.2%	0 0%	0 0%	1 5.3%	1 6.3%	1 6.3%	3 18.8%	3 20%
SD	2 66.7%	3 27.3%	1 25%	0 0%	6 31.6%	1 6.3%	4 25%	7 43.8%	3 20%
PD	1 33.3%	5 45.5%	2 50%	4 100%	11 57.9%	12 75%	11 68.8%	5 31.3%	8 53.3%

4. Secondary Outcome

Title	Median Progression-free Survival Per irRC Based on Kaplan-Meier Product Limit Estimates
Description	PFS was measured from the date of the first dose of study treatment to the date of the first confirmed progression (including clinical progression) or the date of death if a subject died before progression. Per irRC, irPD requires a ≥ 25% increase from nadir in tumor burden at any single time point in two consecutive observations at least 4 weeks apart (Wolchok et al 2009). Subjects who did not experience a PFS event (progression or death) were censored at the date of the last tumor assessment. Subjects with no relevant tumor response assessment were censored at the start date of study treatment.
Time Frame	Up to 36 months

Outcome Measure Data

Analysis Population Description
The population comprises all subjects who received at least one dose of the durvalumab/tremelimumab combination and had the baseline and at least one post-baseline assessment of any efficacy endpoint (clinical or radiological) or a report of death.

Arm/Group Title	Escalation: 0.3 mg/kg Durva + 3 mg/kg Treme	Escalation: 1 mg/kg Durva + 3 mg/kg Treme	Escalation: 3 mg/kg Durva + 3 mg/kg Treme	Escalation: 3 mg/kg Durva + 1 mg/kg Treme	Expansion: Ovarian Cancer	Expansion: Colorectal Cancer	Expansion: Non-triple Negative Breast Cancer	Expansion: Renal Cell Carcinoma	Expansion: Cervical Cancer
Arm/Group Description	Subjects received durvalumab (0.3 mg/kg Q2W for 13 cycles) and tremelimumab (3 mg/kg Q4W for 6 cycles, then Q12W). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W. Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.	Subjects received durvalumab (1 mg/kg Q2W for 13 cycles) and tremelimumab (3 mg/kg Q4W for 6 cycles, then Q12W). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W. Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.	Subjects received durvalumab (3 mg/kg Q2W for 13 cycles) and tremelimumab (3 mg/kg Q4W for 6 cycles, then Q12W). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W. Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.	Subjects received durvalumab (3 mg/kg Q2W for 12 or 13 cycles) and tremelimumab (1 mg/kg Q4W for 6 cycles, then Q12W or Q4W for 4 cycles). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W. Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.	Subjects received durvalumab (10 mg/kg Q2W for 13 cycles or 1500 mg Q4W for 12 cycles) and tremelimumab (1 mg/kg or 75 mg Q4W for 4 cycles). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W. Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.	Subjects received durvalumab (10 mg/kg Q2W for 13 cycles or 1500 mg Q4W for 12 cycles) and tremelimumab (1 mg/kg or 75 mg Q4W for 4 cycles). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W. Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.	Subjects received durvalumab (10 mg/kg Q2W for 13 cycles or 1500 mg Q4W for 12 cycles) and tremelimumab (1 mg/kg or 75 mg Q4W for 4 cycles). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W. Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.	Subjects received durvalumab (10 mg/kg Q2W for 13 cycles or 1500 mg Q4W for 12 cycles) and tremelimumab (1 mg/kg or 75 mg Q4W for 4 cycles). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W. Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.	Subjects received durvalumab (10 mg/kg Q2W for 13 cycles or 1500 mg Q4W for 12 cycles) and tremelimumab (1 mg/kg or 75 mg Q4W for 4 cycles). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W. Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.
Measure Participants	3	10	3	4	18	15	16	15	15
Median (Full Range) [days]	82	76	51	42	54	57	57	326	79

5. Secondary Outcome

Title	Median Progression-free Survival Per RECIST 1.1 Based on Kaplan-Meier Product Limit Estimates
Description	PFS was measured from the date of the first dose of study treatment to the date of the first confirmed progression (including clinical progression) or the date of death if a subject died before progression. Per RECIST 1.1, PD requires a ≥ 20% increase in the sum of the longest diameter of target lesions (Eisenhauer et al 2009). Subjects who did not experience a PFS event (progression or death) were censored at the date of the last tumor assessment. Subjects with no relevant tumor response assessment were censored at the start date of study treatment.
Time Frame	Up to 36 months

Outcome Measure Data

Analysis Population Description
The population comprises all subjects who received at least one dose of the durvalumab/tremelimumab combination and had the baseline and at least one post-baseline assessment of any efficacy endpoint (clinical or radiological) or a report of death.

Arm/Group Title	Escalation: 0.3 mg/kg Durva + 3 mg/kg Treme	Escalation: 1 mg/kg Durva + 3 mg/kg Treme	Escalation: 3 mg/kg Durva + 3 mg/kg Treme	Escalation: 3 mg/kg Durva + 1 mg/kg Treme	Expansion: Ovarian Cancer	Expansion: Colorectal Cancer	Expansion: Non-triple Negative Breast Cancer	Expansion: Renal Cell Carcinoma	Expansion: Cervical Cancer
Arm/Group Description	Subjects received durvalumab (0.3 mg/kg Q2W for 13 cycles) and tremelimumab (3 mg/kg Q4W for 6 cycles, then Q12W). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W. Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.	Subjects received durvalumab (1 mg/kg Q2W for 13 cycles) and tremelimumab (3 mg/kg Q4W for 6 cycles, then Q12W). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W. Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.	Subjects received durvalumab (3 mg/kg Q2W for 13 cycles) and tremelimumab (3 mg/kg Q4W for 6 cycles, then Q12W). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W. Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.	Subjects received durvalumab (3 mg/kg Q2W for 12 or 13 cycles) and tremelimumab (1 mg/kg Q4W for 6 cycles, then Q12W or Q4W for 4 cycles). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W. Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.	Subjects received durvalumab (10 mg/kg Q2W for 13 cycles or 1500 mg Q4W for 12 cycles) and tremelimumab (1 mg/kg or 75 mg Q4W for 4 cycles). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W. Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.	Subjects received durvalumab (10 mg/kg Q2W for 13 cycles or 1500 mg Q4W for 12 cycles) and tremelimumab (1 mg/kg or 75 mg Q4W for 4 cycles). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W. Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.	Subjects received durvalumab (10 mg/kg Q2W for 13 cycles or 1500 mg Q4W for 12 cycles) and tremelimumab (1 mg/kg or 75 mg Q4W for 4 cycles). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W. Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.	Subjects received durvalumab (10 mg/kg Q2W for 13 cycles or 1500 mg Q4W for 12 cycles) and tremelimumab (1 mg/kg or 75 mg Q4W for 4 cycles). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W. Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.	Subjects received durvalumab (10 mg/kg Q2W for 13 cycles or 1500 mg Q4W for 12 cycles) and tremelimumab (1 mg/kg or 75 mg Q4W for 4 cycles). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W. Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.
Measure Participants	3	10	3	4	18	15	16	15	15
Median (Full Range) [days]	82	76	51	42	54	57	56	279	58

6. Secondary Outcome

Title	Median Overall Survival (OS) Based on Kaplan-Meier Product Limit Estimates
Description	All subjects were monitored for survival follow-up at least every 6 months after study completion for up to 3 years after initiation of treatment. Subjects who continued into the Extension part of the study may have been followed for longer than 3 years if they were still receiving treatment. OS was measured from the date of the first dose of study treatment until the recorded date of death. Subjects without a recorded outcome of death were censored at the date of last contact.
Time Frame	Up to 48 months

Outcome Measure Data

Analysis Population Description
The population comprises all subjects who received at least one dose of the durvalumab/tremelimumab combination and had the baseline and at least one post-baseline assessment of any efficacy endpoint (clinical or radiological) or a report of death.

Arm/Group Title	Escalation: 0.3 mg/kg Durva + 3 mg/kg Treme	Escalation: 1 mg/kg Durva + 3 mg/kg Treme	Escalation: 3 mg/kg Durva + 3 mg/kg Treme	Escalation: 3 mg/kg Durva + 1 mg/kg Treme	Expansion: Ovarian Cancer	Expansion: Colorectal Cancer	Expansion: Non-triple Negative Breast Cancer	Expansion: Renal Cell Carcinoma	Expansion: Cervical Cancer
Arm/Group Description	Subjects received durvalumab (0.3 mg/kg Q2W for 13 cycles) and tremelimumab (3 mg/kg Q4W for 6 cycles, then Q12W). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W. Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.	Subjects received durvalumab (1 mg/kg Q2W for 13 cycles) and tremelimumab (3 mg/kg Q4W for 6 cycles, then Q12W). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W. Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.	Subjects received durvalumab (3 mg/kg Q2W for 13 cycles) and tremelimumab (3 mg/kg Q4W for 6 cycles, then Q12W). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W. Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.	Subjects received durvalumab (3 mg/kg Q2W for 12 or 13 cycles) and tremelimumab (1 mg/kg Q4W for 6 cycles, then Q12W or Q4W for 4 cycles). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W. Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.	Subjects received durvalumab (10 mg/kg Q2W for 13 cycles or 1500 mg Q4W for 12 cycles) and tremelimumab (1 mg/kg or 75 mg Q4W for 4 cycles). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W. Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.	Subjects received durvalumab (10 mg/kg Q2W for 13 cycles or 1500 mg Q4W for 12 cycles) and tremelimumab (1 mg/kg or 75 mg Q4W for 4 cycles). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W. Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.	Subjects received durvalumab (10 mg/kg Q2W for 13 cycles or 1500 mg Q4W for 12 cycles) and tremelimumab (1 mg/kg or 75 mg Q4W for 4 cycles). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W. Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.	Subjects received durvalumab (10 mg/kg Q2W for 13 cycles or 1500 mg Q4W for 12 cycles) and tremelimumab (1 mg/kg or 75 mg Q4W for 4 cycles). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W. Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.	Subjects received durvalumab (10 mg/kg Q2W for 13 cycles or 1500 mg Q4W for 12 cycles) and tremelimumab (1 mg/kg or 75 mg Q4W for 4 cycles). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W. Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.
Measure Participants	3	10	3	4	18	15	16	15	15
Median (Full Range) [days]	321	592	664	223	460	267	267	462	583

Adverse Events

	Escalation: 0.3 mg/kg Durva + 3 mg/kg Treme		Escalation: 1 mg/kg Durva + 3 mg/kg Treme		Escalation: 3 mg/kg Durva + 3 mg/kg Treme		Escalation: 3 mg/kg Durva + 1 mg/kg Treme		Expansion: Ovarian Cancer		Expansion: Colorectal Cancer		Expansion: Non-triple Negative Breast Cancer		Expansion: Renal Cell Carcinoma		Expansion: Cervical Cancer
Time Frame	Adverse events (AEs) were documented from informed consent through 90 days after the last study drug dose (regardless of causality to study drug), i.e., during the treatment period, which was up to 15 months for those participating in the Core Study and up to 36 months for those continuing in the Extension. All-cause mortality was collected as a part of survival follow-up for up to 3 years after initiation of treatment, or longer (i.e., up to 48 months) for patients continuing in the Extension.
Adverse Event Reporting Description	AE documentation included onset/resolution dates, severity using the NCI CTCAE (version 4.03), seriousness, relationship to study drug, study drug action taken, treatment, and outcome. In summaries, preferred terms were counted only once per subject at the maximum reported grade.

Arm/Group Title	Escalation: 0.3 mg/kg Durva + 3 mg/kg Treme		Escalation: 1 mg/kg Durva + 3 mg/kg Treme		Escalation: 3 mg/kg Durva + 3 mg/kg Treme		Escalation: 3 mg/kg Durva + 1 mg/kg Treme		Expansion: Ovarian Cancer		Expansion: Colorectal Cancer		Expansion: Non-triple Negative Breast Cancer		Expansion: Renal Cell Carcinoma		Expansion: Cervical Cancer
Arm/Group Description	Subjects received durvalumab (0.3 mg/kg Q2W for 13 cycles) and tremelimumab (3 mg/kg Q4W for 6 cycles, then Q12W). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W. Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.		Subjects received durvalumab (1 mg/kg Q2W for 13 cycles) and tremelimumab (3 mg/kg Q4W for 6 cycles, then Q12W). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W. Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.		Subjects received durvalumab (3 mg/kg Q2W for 13 cycles) and tremelimumab (3 mg/kg Q4W for 6 cycles, then Q12W). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W. Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.		Subjects received durvalumab (3 mg/kg Q2W for 12 or 13 cycles) and tremelimumab (1 mg/kg Q4W for 6 cycles, then Q12W or Q4W for 4 cycles). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W. Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.		Subjects received durvalumab (10 mg/kg Q2W for 13 cycles or 1500 mg Q4W for 12 cycles) and tremelimumab (1 mg/kg or 75 mg Q4W for 4 cycles). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W. Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.		Subjects received durvalumab (10 mg/kg Q2W for 13 cycles or 1500 mg Q4W for 12 cycles) and tremelimumab (1 mg/kg or 75 mg Q4W for 4 cycles). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W. Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.		Subjects received durvalumab (10 mg/kg Q2W for 13 cycles or 1500 mg Q4W for 12 cycles) and tremelimumab (1 mg/kg or 75 mg Q4W for 4 cycles). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W. Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.		Subjects received durvalumab (10 mg/kg Q2W for 13 cycles or 1500 mg Q4W for 12 cycles) and tremelimumab (1 mg/kg or 75 mg Q4W for 4 cycles). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W. Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.		Subjects received durvalumab (10 mg/kg Q2W for 13 cycles or 1500 mg Q4W for 12 cycles) and tremelimumab (1 mg/kg or 75 mg Q4W for 4 cycles). Optional extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg Q4W. Durvalumab and tremelimumab were administered as IV infusions over 60 (± 5) minutes, with durvalumab infusions started at least 60 minutes after the end of the tremelimumab infusion on dual dosing days.
All Cause Mortality
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/3 (100%)		6/11 (54.5%)		4/4 (100%)		3/4 (75%)		10/19 (52.6%)		11/16 (68.8%)		9/16 (56.3%)		4/16 (25%)		7/15 (46.7%)
Serious Adverse Events
	Escalation: 0.3 mg/kg Durva + 3 mg/kg Treme		Escalation: 1 mg/kg Durva + 3 mg/kg Treme		Escalation: 3 mg/kg Durva + 3 mg/kg Treme		Escalation: 3 mg/kg Durva + 1 mg/kg Treme		Expansion: Ovarian Cancer		Expansion: Colorectal Cancer		Expansion: Non-triple Negative Breast Cancer		Expansion: Renal Cell Carcinoma		Expansion: Cervical Cancer
	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	2/3 (66.7%)		5/11 (45.5%)		4/4 (100%)		1/4 (25%)		9/19 (47.4%)		8/16 (50%)		8/16 (50%)		6/16 (37.5%)		8/15 (53.3%)
Blood and lymphatic system disorders
Anaemia	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		1/16 (6.3%)		0/16 (0%)		1/15 (6.7%)
Cardiac disorders
Cardiac disorder	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		1/15 (6.7%)
Pericardial effusion	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		1/19 (5.3%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Sinus tachycardia	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		1/15 (6.7%)
Endocrine disorders
Hypothalamo-pituitary disorder	0/3 (0%)		0/11 (0%)		1/4 (25%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Gastrointestinal disorders
Nausea	1/3 (33.3%)		1/11 (9.1%)		1/4 (25%)		0/4 (0%)		1/19 (5.3%)		3/16 (18.8%)		1/16 (6.3%)		0/16 (0%)		2/15 (13.3%)
Abdominal pain	1/3 (33.3%)		1/11 (9.1%)		1/4 (25%)		0/4 (0%)		1/19 (5.3%)		1/16 (6.3%)		1/16 (6.3%)		0/16 (0%)		3/15 (20%)
Small intestinal obstruction	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		2/19 (10.5%)		1/16 (6.3%)		0/16 (0%)		0/16 (0%)		1/15 (6.7%)
Ascites	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		1/16 (6.3%)		1/16 (6.3%)		0/16 (0%)		1/15 (6.7%)
Diarrhoea	1/3 (33.3%)		0/11 (0%)		1/4 (25%)		0/4 (0%)		0/19 (0%)		1/16 (6.3%)		0/16 (0%)		0/16 (0%)		2/15 (13.3%)
Colitis	0/3 (0%)		1/11 (9.1%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		2/16 (12.5%)		0/16 (0%)		0/15 (0%)
Abdominal distension	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		1/19 (5.3%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Duodenal stenosis	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		1/19 (5.3%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Enterocolitis	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		1/15 (6.7%)
Ileus	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		1/19 (5.3%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Intestinal perforation	0/3 (0%)		0/11 (0%)		1/4 (25%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		1/15 (6.7%)
Pancreatitis	0/3 (0%)		0/11 (0%)		1/4 (25%)		0/4 (0%)		0/19 (0%)		1/16 (6.3%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Vomiting	2/3 (66.7%)		0/11 (0%)		1/4 (25%)		0/4 (0%)		0/19 (0%)		1/16 (6.3%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Constipation	0/3 (0%)		1/11 (9.1%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
General disorders
Pyrexia	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		1/16 (6.3%)		1/16 (6.3%)		0/16 (0%)		1/15 (6.7%)
Pain	0/3 (0%)		0/11 (0%)		1/4 (25%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		1/16 (6.3%)		0/16 (0%)		1/15 (6.7%)
Asthenia	0/3 (0%)		1/11 (9.1%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		1/15 (6.7%)
Multi-organ failure	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		1/16 (6.3%)		0/16 (0%)		0/15 (0%)
Non-cardiac chest pain	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		1/15 (6.7%)
Face oedema	0/3 (0%)		0/11 (0%)		1/4 (25%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Fatigue	1/3 (33.3%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Oedema	0/3 (0%)		1/11 (9.1%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Hepatobiliary disorders
Hyperbilirubinaemia	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		1/19 (5.3%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Infections and infestations
Bacteraemia	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		1/19 (5.3%)		1/16 (6.3%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Pneumonia	0/3 (0%)		2/11 (18.2%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		1/16 (6.3%)		0/16 (0%)		1/16 (6.3%)		0/15 (0%)
Sepsis	0/3 (0%)		1/11 (9.1%)		0/4 (0%)		0/4 (0%)		1/19 (5.3%)		0/16 (0%)		1/16 (6.3%)		0/16 (0%)		0/15 (0%)
Urinary tract infection	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		1/16 (6.3%)		0/16 (0%)		1/15 (6.7%)
Lung infection	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		1/15 (6.7%)
Pyelonephritis	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		1/16 (6.3%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Upper respiratory tract infection	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		1/15 (6.7%)
Kidney infection	0/3 (0%)		0/11 (0%)		1/4 (25%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Peritonitis	0/3 (0%)		0/11 (0%)		1/4 (25%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Vulvitis	0/3 (0%)		0/11 (0%)		1/4 (25%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Injury, poisoning and procedural complications
Accidental overdose	0/3 (0%)		0/11 (0%)		1/4 (25%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Investigations
Lipase increased	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		1/16 (6.3%)		0/16 (0%)		1/16 (6.3%)		0/15 (0%)
Alanine aminotransferase increased	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		1/16 (6.3%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Amylase increased	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		1/16 (6.3%)		0/15 (0%)
Aspartate aminotransferase increased	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		1/16 (6.3%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Blood creatinine increased	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		1/15 (6.7%)
Platelet count decreased	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		1/16 (6.3%)		0/16 (0%)		0/15 (0%)
Liver function test abnormal	0/3 (0%)		0/11 (0%)		1/4 (25%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Metabolism and nutrition disorders
Decreased appetite	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		1/16 (6.3%)		0/16 (0%)		0/16 (0%)		1/15 (6.7%)
Dehydration	1/3 (33.3%)		2/11 (18.2%)		0/4 (0%)		0/4 (0%)		1/19 (5.3%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		1/15 (6.7%)
Hypercalcaemia	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		1/16 (6.3%)		1/16 (6.3%)		0/15 (0%)
Hypokalaemia	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		1/16 (6.3%)		0/16 (0%)		0/15 (0%)
Hyponatraemia	0/3 (0%)		0/11 (0%)		1/4 (25%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Musculoskeletal and connective tissue disorders
Back pain	0/3 (0%)		0/11 (0%)		1/4 (25%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		2/15 (13.3%)
Arthralgia	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		1/16 (6.3%)		0/15 (0%)
Muscular weakness	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		1/16 (6.3%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Musculoskeletal pain	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		1/16 (6.3%)		0/15 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant neoplasm progression	1/3 (33.3%)		3/11 (27.3%)		0/4 (0%)		0/4 (0%)		3/19 (15.8%)		3/16 (18.8%)		0/16 (0%)		0/16 (0%)		1/15 (6.7%)
Brain neoplasm malignant	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		1/16 (6.3%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Nervous system disorders
Cerebral infarction	0/3 (0%)		0/11 (0%)		0/4 (0%)		1/4 (25%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Psychiatric disorders
Confusional state	0/3 (0%)		1/11 (9.1%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		1/15 (6.7%)
Mental status changes	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		1/16 (6.3%)		0/16 (0%)		0/15 (0%)
Agitation	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		1/15 (6.7%)
Renal and urinary disorders
Haematuria	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		1/16 (6.3%)		0/16 (0%)		1/15 (6.7%)
Hydronephrosis	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		1/16 (6.3%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Renal failure acute	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		1/15 (6.7%)
Urinary tract obstruction	0/3 (0%)		0/11 (0%)		1/4 (25%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Reproductive system and breast disorders
Vaginal fistula	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		1/16 (6.3%)		0/16 (0%)		0/16 (0%)		1/15 (6.7%)
Respiratory, thoracic and mediastinal disorders
Pleural effusion	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		2/16 (12.5%)		0/16 (0%)		2/15 (13.3%)
Hypoxia	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		1/16 (6.3%)		1/16 (6.3%)		0/15 (0%)
Bronchial obstruction	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		1/19 (5.3%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Pneumonitis	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		1/16 (6.3%)		0/15 (0%)
Aspiration	0/3 (0%)		0/11 (0%)		1/4 (25%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Dyspnoea	0/3 (0%)		1/11 (9.1%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Laryngeal oedema	0/3 (0%)		0/11 (0%)		1/4 (25%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Vascular disorders
Embolism	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		1/16 (6.3%)		0/16 (0%)		0/15 (0%)
Lymphoedema	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		1/16 (6.3%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Other (Not Including Serious) Adverse Events
	Escalation: 0.3 mg/kg Durva + 3 mg/kg Treme		Escalation: 1 mg/kg Durva + 3 mg/kg Treme		Escalation: 3 mg/kg Durva + 3 mg/kg Treme		Escalation: 3 mg/kg Durva + 1 mg/kg Treme		Expansion: Ovarian Cancer		Expansion: Colorectal Cancer		Expansion: Non-triple Negative Breast Cancer		Expansion: Renal Cell Carcinoma		Expansion: Cervical Cancer
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/3 (100%)		11/11 (100%)		4/4 (100%)		4/4 (100%)		19/19 (100%)		16/16 (100%)		16/16 (100%)		16/16 (100%)		15/15 (100%)
Blood and lymphatic system disorders
Anaemia	2/3 (66.7%)		6/11 (54.5%)		0/4 (0%)		1/4 (25%)		3/19 (15.8%)		1/16 (6.3%)		3/16 (18.8%)		1/16 (6.3%)		2/15 (13.3%)
Lymph node pain	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		2/19 (10.5%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Thrombocytopenia	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		1/16 (6.3%)		1/16 (6.3%)		0/16 (0%)		0/15 (0%)
Lymphadenopathy	0/3 (0%)		0/11 (0%)		1/4 (25%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Cardiac disorders
Tachycardia	0/3 (0%)		1/11 (9.1%)		0/4 (0%)		0/4 (0%)		1/19 (5.3%)		0/16 (0%)		1/16 (6.3%)		0/16 (0%)		2/15 (13.3%)
Pericardial effusion	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		1/16 (6.3%)		0/16 (0%)		0/15 (0%)
Sinus tachycardia	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		1/15 (6.7%)
Palpitations	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		1/19 (5.3%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Angina pectoris	0/3 (0%)		1/11 (9.1%)		1/4 (25%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Ear and labyrinth disorders
Ear discomfort	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		1/19 (5.3%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Tinnitus	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		1/16 (6.3%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Vertigo	0/3 (0%)		1/11 (9.1%)		0/4 (0%)		0/4 (0%)		1/19 (5.3%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Endocrine disorders
Hypothyroidism	0/3 (0%)		2/11 (18.2%)		0/4 (0%)		0/4 (0%)		2/19 (10.5%)		3/16 (18.8%)		1/16 (6.3%)		2/16 (12.5%)		2/15 (13.3%)
Hyperthyroidism	0/3 (0%)		1/11 (9.1%)		0/4 (0%)		0/4 (0%)		2/19 (10.5%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		1/15 (6.7%)
Adrenal insufficiency	0/3 (0%)		1/11 (9.1%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		1/16 (6.3%)		0/15 (0%)
Hypophysitis	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		1/19 (5.3%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Eye disorders
Vitreous floaters	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		1/16 (6.3%)		0/16 (0%)		0/16 (0%)		1/15 (6.7%)
Dry eye	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		1/16 (6.3%)		0/15 (0%)
Lacrimation increased	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		1/19 (5.3%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Ocular hyperaemia	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		1/16 (6.3%)		0/15 (0%)
Vision blurred	0/3 (0%)		1/11 (9.1%)		0/4 (0%)		1/4 (25%)		0/19 (0%)		1/16 (6.3%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Visual impairment	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		1/16 (6.3%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Cataract	0/3 (0%)		0/11 (0%)		0/4 (0%)		1/4 (25%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Eye irritation	0/3 (0%)		1/11 (9.1%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Gastrointestinal disorders
Nausea	0/3 (0%)		3/11 (27.3%)		1/4 (25%)		1/4 (25%)		3/19 (15.8%)		3/16 (18.8%)		6/16 (37.5%)		5/16 (31.3%)		3/15 (20%)
Diarrhoea	1/3 (33.3%)		8/11 (72.7%)		0/4 (0%)		2/4 (50%)		8/19 (42.1%)		4/16 (25%)		7/16 (43.8%)		1/16 (6.3%)		3/15 (20%)
Vomiting	0/3 (0%)		5/11 (45.5%)		2/4 (50%)		0/4 (0%)		7/19 (36.8%)		6/16 (37.5%)		4/16 (25%)		2/16 (12.5%)		4/15 (26.7%)
Constipation	1/3 (33.3%)		5/11 (45.5%)		0/4 (0%)		0/4 (0%)		2/19 (10.5%)		5/16 (31.3%)		4/16 (25%)		3/16 (18.8%)		5/15 (33.3%)
Abdominal pain	0/3 (0%)		1/11 (9.1%)		1/4 (25%)		2/4 (50%)		3/19 (15.8%)		5/16 (31.3%)		3/16 (18.8%)		0/16 (0%)		0/15 (0%)
Dry mouth	0/3 (0%)		3/11 (27.3%)		1/4 (25%)		0/4 (0%)		1/19 (5.3%)		1/16 (6.3%)		0/16 (0%)		1/16 (6.3%)		3/15 (20%)
Ascites	1/3 (33.3%)		1/11 (9.1%)		1/4 (25%)		1/4 (25%)		0/19 (0%)		1/16 (6.3%)		0/16 (0%)		0/16 (0%)		1/15 (6.7%)
Small intestinal obstruction	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		1/19 (5.3%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Abdominal distension	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		3/16 (18.8%)		0/16 (0%)		0/15 (0%)
Gastrooesophageal reflux disease	1/3 (33.3%)		1/11 (9.1%)		0/4 (0%)		0/4 (0%)		1/19 (5.3%)		0/16 (0%)		2/16 (12.5%)		0/16 (0%)		1/15 (6.7%)
Colitis	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		1/19 (5.3%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Abdominal pain upper	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		2/16 (12.5%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Dysphagia	0/3 (0%)		1/11 (9.1%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		1/16 (6.3%)		1/16 (6.3%)		0/15 (0%)
Flatulence	1/3 (33.3%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		2/15 (13.3%)
Abdominal pain lower	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		1/16 (6.3%)		0/15 (0%)
Dyspepsia	0/3 (0%)		0/11 (0%)		0/4 (0%)		2/4 (50%)		0/19 (0%)		1/16 (6.3%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Gastrointestinal haemorrhage	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		1/15 (6.7%)
Haematochezia	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		1/15 (6.7%)
Haemorrhoids	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		1/16 (6.3%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Rectal tenesmus	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		1/16 (6.3%)		0/16 (0%)		0/15 (0%)
Retching	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		1/16 (6.3%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Salivary gland calculus	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		1/19 (5.3%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Abdominal discomfort	0/3 (0%)		0/11 (0%)		1/4 (25%)		1/4 (25%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Toothache	0/3 (0%)		1/11 (9.1%)		1/4 (25%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Gastric ulcer	0/3 (0%)		1/11 (9.1%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Mouth ulceration	0/3 (0%)		0/11 (0%)		0/4 (0%)		1/4 (25%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Oral pain	0/3 (0%)		0/11 (0%)		1/4 (25%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
General disorders
Fatigue	1/3 (33.3%)		5/11 (45.5%)		2/4 (50%)		3/4 (75%)		11/19 (57.9%)		8/16 (50%)		7/16 (43.8%)		8/16 (50%)		7/15 (46.7%)
Pyrexia	0/3 (0%)		1/11 (9.1%)		1/4 (25%)		0/4 (0%)		2/19 (10.5%)		2/16 (12.5%)		1/16 (6.3%)		2/16 (12.5%)		5/15 (33.3%)
Oedema peripheral	2/3 (66.7%)		3/11 (27.3%)		1/4 (25%)		0/4 (0%)		2/19 (10.5%)		3/16 (18.8%)		3/16 (18.8%)		3/16 (18.8%)		3/15 (20%)
Asthenia	0/3 (0%)		4/11 (36.4%)		1/4 (25%)		0/4 (0%)		2/19 (10.5%)		1/16 (6.3%)		2/16 (12.5%)		0/16 (0%)		1/15 (6.7%)
Chills	1/3 (33.3%)		2/11 (18.2%)		1/4 (25%)		1/4 (25%)		1/19 (5.3%)		1/16 (6.3%)		1/16 (6.3%)		2/16 (12.5%)		2/15 (13.3%)
Influenza like illness	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		1/16 (6.3%)		1/16 (6.3%)		4/15 (26.7%)
Malaise	0/3 (0%)		1/11 (9.1%)		0/4 (0%)		0/4 (0%)		1/19 (5.3%)		0/16 (0%)		0/16 (0%)		3/16 (18.8%)		1/15 (6.7%)
Device occlusion	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		2/19 (10.5%)		1/16 (6.3%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Early satiety	0/3 (0%)		1/11 (9.1%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		1/16 (6.3%)		1/16 (6.3%)		0/16 (0%)		1/15 (6.7%)
Infusion site reaction	0/3 (0%)		1/11 (9.1%)		0/4 (0%)		0/4 (0%)		1/19 (5.3%)		0/16 (0%)		1/16 (6.3%)		0/16 (0%)		1/15 (6.7%)
Non-cardiac chest pain	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		1/16 (6.3%)		1/16 (6.3%)		0/15 (0%)
Pain	0/3 (0%)		1/11 (9.1%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		1/16 (6.3%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Mucosal inflammation	0/3 (0%)		1/11 (9.1%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		1/16 (6.3%)		0/16 (0%)		1/15 (6.7%)
Swelling	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		2/19 (10.5%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Irritability	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		1/16 (6.3%)		0/16 (0%)		0/15 (0%)
Localised oedema	0/3 (0%)		1/11 (9.1%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		1/16 (6.3%)		0/15 (0%)
Oedema	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		1/15 (6.7%)
Thirst	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		1/15 (6.7%)
Face oedema	0/3 (0%)		1/11 (9.1%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Tenderness	0/3 (0%)		1/11 (9.1%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Facial pain	0/3 (0%)		1/11 (9.1%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Hepatobiliary disorders
Hyperbilirubinaemia	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		1/16 (6.3%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Hepatic failure	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		1/16 (6.3%)		0/16 (0%)		0/15 (0%)
Hepatitis	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		1/16 (6.3%)		0/16 (0%)		0/15 (0%)
Immune system disorders
Contrast media allergy	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		1/15 (6.7%)
Drug hypersensitivity	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		1/16 (6.3%)		0/16 (0%)		0/15 (0%)
Seasonal allergy	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		1/16 (6.3%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Infections and infestations
Urinary tract infection	0/3 (0%)		2/11 (18.2%)		0/4 (0%)		0/4 (0%)		1/19 (5.3%)		2/16 (12.5%)		0/16 (0%)		0/16 (0%)		5/15 (33.3%)
Upper respiratory tract infection	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		1/19 (5.3%)		1/16 (6.3%)		1/16 (6.3%)		1/16 (6.3%)		1/15 (6.7%)
Pneumonia	0/3 (0%)		0/11 (0%)		0/4 (0%)		1/4 (25%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		1/16 (6.3%)		0/15 (0%)
Candidiasis	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		1/19 (5.3%)		0/16 (0%)		1/16 (6.3%)		0/16 (0%)		0/15 (0%)
Cystitis	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		2/15 (13.3%)
Lung infection	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		1/16 (6.3%)		0/15 (0%)
Oral candidiasis	0/3 (0%)		0/11 (0%)		0/4 (0%)		1/4 (25%)		0/19 (0%)		1/16 (6.3%)		0/16 (0%)		0/16 (0%)		1/15 (6.7%)
Abscess oral	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		1/19 (5.3%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Bacteriuria	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		1/15 (6.7%)
Bronchitis	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		1/15 (6.7%)
Cellulitis	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		1/15 (6.7%)
Fungal infection	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		1/16 (6.3%)		0/16 (0%)		0/15 (0%)
Lyme disease	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		1/16 (6.3%)		0/15 (0%)
Onychomycosis	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		1/16 (6.3%)		0/16 (0%)		0/15 (0%)
Sinusitis	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		1/16 (6.3%)		0/16 (0%)		0/15 (0%)
Tinea pedis	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		1/16 (6.3%)		0/16 (0%)		0/15 (0%)
Genital herpes	1/3 (33.3%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Herpes zoster	0/3 (0%)		0/11 (0%)		0/4 (0%)		1/4 (25%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Mucosal infection	0/3 (0%)		0/11 (0%)		1/4 (25%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Pneumonia staphylococcal	0/3 (0%)		1/11 (9.1%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Injury, poisoning and procedural complications
Fall	0/3 (0%)		1/11 (9.1%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		1/16 (6.3%)		1/16 (6.3%)		0/15 (0%)
Contusion	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		1/16 (6.3%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Fracture	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		1/16 (6.3%)		0/15 (0%)
Procedural pain	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		1/19 (5.3%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Radius fracture	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		1/16 (6.3%)		0/16 (0%)		0/15 (0%)
Wound	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		1/15 (6.7%)
Acetabulum fracture	0/3 (0%)		1/11 (9.1%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Investigations
Aspartate aminotransferase increased	0/3 (0%)		2/11 (18.2%)		0/4 (0%)		1/4 (25%)		2/19 (10.5%)		1/16 (6.3%)		4/16 (25%)		3/16 (18.8%)		2/15 (13.3%)
Weight decreased	0/3 (0%)		3/11 (27.3%)		0/4 (0%)		0/4 (0%)		4/19 (21.1%)		3/16 (18.8%)		1/16 (6.3%)		1/16 (6.3%)		2/15 (13.3%)
Blood alkaline phosphatase increased	0/3 (0%)		1/11 (9.1%)		0/4 (0%)		0/4 (0%)		3/19 (15.8%)		2/16 (12.5%)		2/16 (12.5%)		0/16 (0%)		2/15 (13.3%)
Alanine aminotransferase increased	0/3 (0%)		2/11 (18.2%)		0/4 (0%)		1/4 (25%)		1/19 (5.3%)		0/16 (0%)		2/16 (12.5%)		2/16 (12.5%)		2/15 (13.3%)
Blood creatinine increased	0/3 (0%)		2/11 (18.2%)		0/4 (0%)		1/4 (25%)		1/19 (5.3%)		0/16 (0%)		0/16 (0%)		1/16 (6.3%)		1/15 (6.7%)
Lipase increased	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		1/16 (6.3%)		0/15 (0%)
Amylase increased	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		1/16 (6.3%)		0/15 (0%)
Blood bilirubin increased	0/3 (0%)		1/11 (9.1%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		1/16 (6.3%)		0/16 (0%)		1/15 (6.7%)
International normalised ratio increased	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		1/16 (6.3%)		1/16 (6.3%)		0/16 (0%)		0/15 (0%)
White blood cell count decreased	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		2/16 (12.5%)		0/16 (0%)		0/15 (0%)
Bilirubin conjugated increased	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		1/19 (5.3%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Blood lactate dehydrogenase increased	0/3 (0%)		1/11 (9.1%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		1/15 (6.7%)
Blood potassium decreased	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		1/19 (5.3%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Blood sodium decreased	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		1/19 (5.3%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Blood thyroid stimulating hormone increased	0/3 (0%)		0/11 (0%)		1/4 (25%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		1/16 (6.3%)		0/15 (0%)
Neutrophil count increased	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		1/15 (6.7%)
White blood cell count increased	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		1/15 (6.7%)
Lymphocyte count decreased	0/3 (0%)		1/11 (9.1%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Urine output decreased	0/3 (0%)		0/11 (0%)		0/4 (0%)		1/4 (25%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Metabolism and nutrition disorders
Decreased appetite	1/3 (33.3%)		5/11 (45.5%)		1/4 (25%)		0/4 (0%)		4/19 (21.1%)		5/16 (31.3%)		4/16 (25%)		5/16 (31.3%)		5/15 (33.3%)
Dehydration	0/3 (0%)		1/11 (9.1%)		0/4 (0%)		0/4 (0%)		2/19 (10.5%)		3/16 (18.8%)		3/16 (18.8%)		0/16 (0%)		0/15 (0%)
Hypoalbuminaemia	1/3 (33.3%)		2/11 (18.2%)		0/4 (0%)		0/4 (0%)		1/19 (5.3%)		2/16 (12.5%)		2/16 (12.5%)		0/16 (0%)		1/15 (6.7%)
Hyponatraemia	1/3 (33.3%)		3/11 (27.3%)		0/4 (0%)		0/4 (0%)		2/19 (10.5%)		1/16 (6.3%)		2/16 (12.5%)		0/16 (0%)		1/15 (6.7%)
Hypokalaemia	0/3 (0%)		2/11 (18.2%)		0/4 (0%)		0/4 (0%)		3/19 (15.8%)		0/16 (0%)		1/16 (6.3%)		0/16 (0%)		0/15 (0%)
Hypercalcaemia	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		1/16 (6.3%)		0/15 (0%)
Hyperglycaemia	0/3 (0%)		3/11 (27.3%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		2/16 (12.5%)		0/16 (0%)		1/15 (6.7%)
Hypocalcaemia	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		2/16 (12.5%)		0/16 (0%)		0/15 (0%)
Hyperkalaemia	1/3 (33.3%)		1/11 (9.1%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		1/15 (6.7%)
Hypernatraemia	0/3 (0%)		1/11 (9.1%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		1/16 (6.3%)		0/16 (0%)		0/15 (0%)
Hypophosphataemia	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		1/15 (6.7%)
Polydipsia	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		1/16 (6.3%)		0/16 (0%)		0/15 (0%)
Hypomagnesaemia	0/3 (0%)		1/11 (9.1%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/3 (0%)		3/11 (27.3%)		0/4 (0%)		0/4 (0%)		3/19 (15.8%)		2/16 (12.5%)		3/16 (18.8%)		2/16 (12.5%)		1/15 (6.7%)
Back pain	2/3 (66.7%)		5/11 (45.5%)		1/4 (25%)		1/4 (25%)		2/19 (10.5%)		2/16 (12.5%)		1/16 (6.3%)		1/16 (6.3%)		1/15 (6.7%)
Myalgia	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		2/19 (10.5%)		1/16 (6.3%)		0/16 (0%)		2/16 (12.5%)		2/15 (13.3%)
Muscular weakness	0/3 (0%)		1/11 (9.1%)		0/4 (0%)		0/4 (0%)		1/19 (5.3%)		0/16 (0%)		2/16 (12.5%)		0/16 (0%)		1/15 (6.7%)
Muscle spasms	0/3 (0%)		1/11 (9.1%)		1/4 (25%)		0/4 (0%)		3/19 (15.8%)		0/16 (0%)		1/16 (6.3%)		0/16 (0%)		0/15 (0%)
Pain in extremity	0/3 (0%)		1/11 (9.1%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		1/16 (6.3%)		1/16 (6.3%)		2/16 (12.5%)		0/15 (0%)
Musculoskeletal chest pain	0/3 (0%)		1/11 (9.1%)		0/4 (0%)		0/4 (0%)		1/19 (5.3%)		0/16 (0%)		1/16 (6.3%)		0/16 (0%)		1/15 (6.7%)
Musculoskeletal pain	0/3 (0%)		2/11 (18.2%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		1/16 (6.3%)		0/16 (0%)		0/16 (0%)		1/15 (6.7%)
Neck pain	0/3 (0%)		1/11 (9.1%)		0/4 (0%)		0/4 (0%)		2/19 (10.5%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Arthritis	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		1/19 (5.3%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Flank pain	0/3 (0%)		1/11 (9.1%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		1/15 (6.7%)
Joint effusion	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		1/19 (5.3%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Muscle tightness	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		1/19 (5.3%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Groin pain	0/3 (0%)		2/11 (18.2%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Joint swelling	0/3 (0%)		1/11 (9.1%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Pathological fracture	0/3 (0%)		1/11 (9.1%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Nervous system disorders
Dizziness	1/3 (33.3%)		0/11 (0%)		1/4 (25%)		0/4 (0%)		3/19 (15.8%)		3/16 (18.8%)		1/16 (6.3%)		0/16 (0%)		0/15 (0%)
Dysgeusia	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		2/16 (12.5%)		0/16 (0%)		0/16 (0%)		2/15 (13.3%)
Headache	1/3 (33.3%)		1/11 (9.1%)		1/4 (25%)		0/4 (0%)		0/19 (0%)		2/16 (12.5%)		1/16 (6.3%)		0/16 (0%)		1/15 (6.7%)
Paraesthesia	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		2/19 (10.5%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		1/15 (6.7%)
Akathisia	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		1/15 (6.7%)
Cognitive disorder	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		1/19 (5.3%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Disturbance in attention	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		1/19 (5.3%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Dizziness postural	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		1/19 (5.3%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Hypoaesthesia	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		1/19 (5.3%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Memory impairment	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		1/19 (5.3%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Monoplegia	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		1/16 (6.3%)		0/16 (0%)		0/15 (0%)
Neuralgia	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		1/16 (6.3%)		0/15 (0%)
Neuropathy peripheral	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		1/19 (5.3%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Presyncope	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		1/19 (5.3%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Sciatica	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		1/16 (6.3%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Sensory disturbance	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		1/16 (6.3%)		0/16 (0%)		0/15 (0%)
Speech disorder	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		1/16 (6.3%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Tremor	0/3 (0%)		0/11 (0%)		1/4 (25%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		1/16 (6.3%)		0/15 (0%)
Paralysis	0/3 (0%)		1/11 (9.1%)		0/4 (0%)		1/4 (25%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Amnesia	0/3 (0%)		0/11 (0%)		0/4 (0%)		1/4 (25%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Peripheral sensory neuropathy	0/3 (0%)		1/11 (9.1%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Psychiatric disorders
Anxiety	0/3 (0%)		0/11 (0%)		1/4 (25%)		0/4 (0%)		3/19 (15.8%)		3/16 (18.8%)		2/16 (12.5%)		0/16 (0%)		2/15 (13.3%)
Insomnia	0/3 (0%)		1/11 (9.1%)		1/4 (25%)		1/4 (25%)		4/19 (21.1%)		3/16 (18.8%)		1/16 (6.3%)		1/16 (6.3%)		0/15 (0%)
Confusional state	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		1/19 (5.3%)		1/16 (6.3%)		1/16 (6.3%)		0/16 (0%)		0/15 (0%)
Depression	0/3 (0%)		1/11 (9.1%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		2/16 (12.5%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Mental status changes	0/3 (0%)		1/11 (9.1%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		1/16 (6.3%)		0/16 (0%)		0/15 (0%)
Euphoric mood	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		1/16 (6.3%)		0/16 (0%)		0/15 (0%)
Agitation	0/3 (0%)		0/11 (0%)		0/4 (0%)		1/4 (25%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Renal and urinary disorders
Haematuria	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		1/19 (5.3%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		2/15 (13.3%)
Bladder spasm	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		1/16 (6.3%)		0/16 (0%)		1/15 (6.7%)
Dysuria	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		2/15 (13.3%)
Hydronephrosis	1/3 (33.3%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		1/15 (6.7%)
Proteinuria	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		1/19 (5.3%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		1/15 (6.7%)
Incontinence	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		1/15 (6.7%)
Nocturia	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		1/15 (6.7%)
Pollakiuria	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		1/15 (6.7%)
Pyuria	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		1/15 (6.7%)
Urinary retention	0/3 (0%)		1/11 (9.1%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		1/15 (6.7%)
Urinary tract pain	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		1/15 (6.7%)
Urine abnormality	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		1/16 (6.3%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Nephrolithiasis	0/3 (0%)		1/11 (9.1%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Urinary incontinence	0/3 (0%)		0/11 (0%)		1/4 (25%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Reproductive system and breast disorders
Vaginal fistula	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		1/15 (6.7%)
Vaginal haemorrhage	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		1/19 (5.3%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		2/15 (13.3%)
Menorrhagia	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		1/16 (6.3%)		1/15 (6.7%)
Vaginal discharge	0/3 (0%)		0/11 (0%)		1/4 (25%)		0/4 (0%)		0/19 (0%)		1/16 (6.3%)		0/16 (0%)		0/16 (0%)		1/15 (6.7%)
Pelvic discomfort	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		1/19 (5.3%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Pelvic pain	0/3 (0%)		0/11 (0%)		1/4 (25%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		1/15 (6.7%)
Vaginal disorder	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		1/15 (6.7%)
Vulvovaginal pruritus	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		1/16 (6.3%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	1/3 (33.3%)		3/11 (27.3%)		1/4 (25%)		0/4 (0%)		4/19 (21.1%)		2/16 (12.5%)		3/16 (18.8%)		3/16 (18.8%)		2/15 (13.3%)
Dyspnoea	1/3 (33.3%)		1/11 (9.1%)		0/4 (0%)		0/4 (0%)		4/19 (21.1%)		2/16 (12.5%)		2/16 (12.5%)		2/16 (12.5%)		2/15 (13.3%)
Nasal congestion	1/3 (33.3%)		1/11 (9.1%)		0/4 (0%)		0/4 (0%)		2/19 (10.5%)		2/16 (12.5%)		1/16 (6.3%)		1/16 (6.3%)		1/15 (6.7%)
Pleural effusion	0/3 (0%)		0/11 (0%)		1/4 (25%)		0/4 (0%)		2/19 (10.5%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Productive cough	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		1/16 (6.3%)		1/16 (6.3%)		3/16 (18.8%)		0/15 (0%)
Oropharyngeal pain	0/3 (0%)		2/11 (18.2%)		1/4 (25%)		0/4 (0%)		1/19 (5.3%)		0/16 (0%)		0/16 (0%)		1/16 (6.3%)		2/15 (13.3%)
Dysphonia	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		1/19 (5.3%)		1/16 (6.3%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Dyspnoea exertional	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		1/16 (6.3%)		1/16 (6.3%)		0/15 (0%)
Upper-airway cough syndrome	0/3 (0%)		1/11 (9.1%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		1/16 (6.3%)		0/16 (0%)		1/16 (6.3%)		0/15 (0%)
Emphysema	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		1/16 (6.3%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Pleuritic pain	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		1/15 (6.7%)
Pulmonary embolism	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		1/19 (5.3%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Rhinorrhoea	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		1/15 (6.7%)
Epistaxis	0/3 (0%)		1/11 (9.1%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Haemoptysis	0/3 (0%)		1/11 (9.1%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Pneumonitis	0/3 (0%)		0/11 (0%)		1/4 (25%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Sinus congestion	1/3 (33.3%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Upper respiratory tract congestion	0/3 (0%)		1/11 (9.1%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Skin and subcutaneous tissue disorders
Pruritus	1/3 (33.3%)		2/11 (18.2%)		2/4 (50%)		1/4 (25%)		4/19 (21.1%)		3/16 (18.8%)		2/16 (12.5%)		3/16 (18.8%)		3/15 (20%)
Rash	2/3 (66.7%)		1/11 (9.1%)		1/4 (25%)		0/4 (0%)		1/19 (5.3%)		3/16 (18.8%)		0/16 (0%)		4/16 (25%)		3/15 (20%)
Rash maculo-papular	0/3 (0%)		2/11 (18.2%)		0/4 (0%)		1/4 (25%)		4/19 (21.1%)		0/16 (0%)		1/16 (6.3%)		5/16 (31.3%)		1/15 (6.7%)
Dry skin	0/3 (0%)		1/11 (9.1%)		0/4 (0%)		1/4 (25%)		0/19 (0%)		1/16 (6.3%)		2/16 (12.5%)		2/16 (12.5%)		0/15 (0%)
Erythema	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		1/19 (5.3%)		0/16 (0%)		1/16 (6.3%)		1/16 (6.3%)		0/15 (0%)
Hyperhidrosis	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		1/19 (5.3%)		0/16 (0%)		1/16 (6.3%)		0/16 (0%)		1/15 (6.7%)
Night sweats	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		2/16 (12.5%)		1/16 (6.3%)		0/16 (0%)		0/15 (0%)
Rash papular	0/3 (0%)		0/11 (0%)		1/4 (25%)		1/4 (25%)		1/19 (5.3%)		1/16 (6.3%)		1/16 (6.3%)		0/16 (0%)		0/15 (0%)
Dermatitis acneiform	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		2/19 (10.5%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Dyshidrotic eczema	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		1/16 (6.3%)		0/16 (0%)		0/15 (0%)
Eczema	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		1/19 (5.3%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Livedo reticularis	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		1/15 (6.7%)
Rash erythematous	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		1/16 (6.3%)		0/16 (0%)		0/15 (0%)
Rash generalised	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		1/15 (6.7%)
Rash pruritic	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		1/16 (6.3%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Skin exfoliation	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		1/16 (6.3%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Skin striae	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		1/16 (6.3%)		0/16 (0%)		0/15 (0%)
Swelling face	0/3 (0%)		1/11 (9.1%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Vascular disorders
Hypotension	0/3 (0%)		2/11 (18.2%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		1/16 (6.3%)		0/16 (0%)		1/16 (6.3%)		2/15 (13.3%)
Hot flush	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		1/16 (6.3%)		1/16 (6.3%)		1/16 (6.3%)		0/15 (0%)
Hypertension	0/3 (0%)		2/11 (18.2%)		0/4 (0%)		0/4 (0%)		1/19 (5.3%)		1/16 (6.3%)		0/16 (0%)		1/16 (6.3%)		0/15 (0%)
Embolism	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		1/16 (6.3%)		0/16 (0%)		0/16 (0%)		0/15 (0%)
Lymphoedema	0/3 (0%)		0/11 (0%)		1/4 (25%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		1/15 (6.7%)
Thrombophlebitis	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		1/16 (6.3%)		0/16 (0%)		1/16 (6.3%)		0/15 (0%)
Orthostatic hypotension	0/3 (0%)		0/11 (0%)		0/4 (0%)		0/4 (0%)		0/19 (0%)		0/16 (0%)		1/16 (6.3%)		0/16 (0%)		0/15 (0%)
Haematoma	0/3 (0%)		0/11 (0%)		0/4 (0%)		1/4 (25%)		0/19 (0%)		0/16 (0%)		0/16 (0%)		0/16 (0%)		0/15 (0%)

Limitations/Caveats

[Not Specified]

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Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.

Results Point of Contact

Name/Title	Mary Macri, Director, Clinical Trials Management
Organization	Ludwig Institute for Cancer Research
Phone	(212) 450-1546
Email	mmacri@lcr.org

Responsible Party:

Ludwig Institute for Cancer Research

ClinicalTrials.gov Identifier:

NCT01975831

Other Study ID Numbers:

LUD2013-003

First Posted:

Nov 5, 2013

Last Update Posted:

Jul 15, 2021

Last Verified:

Jul 1, 2021

A Phase 1 Study to Evaluate MEDI4736 in Combination With Tremelimumab

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