Trial Outcomes & Findings for Study to Evaluate the Safety and Efficacy of Two Different Dosing Schedules of Pembrolizumab (MK-3475) Compared to Ipilimumab in Participants With Advanced Melanoma (MK-3475-006/KEYNOTE-006) (NCT NCT01866319)

Last Updated: 2020-06-02

Results Overview

PFS was defined as the time from randomization to the first documented disease progression, based on blinded Independent Radiology plus Oncology review (IRO) using RECIST 1.1, or death due to any cause, whichever occurred first. Disease progression was defined as a 20% or greater increase in the sum of diameters of target lesions with an absolute increase of at least 5 mm or the appearance of new lesions. The primary analysis of PFS was performed at the time of the first protocol pre-specified statistical analysis, with data cut-off of 03-Sep-2014.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

834 participants

Primary outcome timeframe

Up to approximately 12 months (through first pre-specified statistical analysis cut-off date of 03-Sep-2014)

Results posted on

2020-06-02

Participant Flow

Participants with advanced melanoma were recruited to receive ipilimumab once every 3 weeks (Q3W), or a primary course of pembrolizumab administered every 2 weeks (Q2W) or every 3 weeks (Q3W).

834 participants were randomized 1:1:1 to receive ipilimumab Q3W, pembrolizumab Q2W, or pembrolizumab Q3W. For participants receiving pembrolizumab, all safety and efficacy results data reported are for the primary pembrolizumab course received.

Participant milestones

Participant milestones
Measure	Ipilimumab Participants received ipilimumab, 3 mg/kg intravenously (IV), once every 3 weeks (Q3W) for a total of 4 doses (up to approximately 3 months).	Pembrolizumab Q2W Participants received pembrolizumab, 10 mg/kg IV, once every 2 weeks (Q2W) for up to approximately 24 months.	Pembrolizumab Q3W Participants received pembrolizumab, 10 mg/kg IV, Q3W for up to approximately 24 months.
Overall Study STARTED	278	279	277
Overall Study Treated	256	278	277
Overall Study COMPLETED	71	101	97
Overall Study NOT COMPLETED	207	178	180

Reasons for withdrawal

Reasons for withdrawal
Measure	Ipilimumab Participants received ipilimumab, 3 mg/kg intravenously (IV), once every 3 weeks (Q3W) for a total of 4 doses (up to approximately 3 months).	Pembrolizumab Q2W Participants received pembrolizumab, 10 mg/kg IV, once every 2 weeks (Q2W) for up to approximately 24 months.	Pembrolizumab Q3W Participants received pembrolizumab, 10 mg/kg IV, Q3W for up to approximately 24 months.
Overall Study Adverse Event	12	5	9
Overall Study Clinical progression	3	2	2
Overall Study Death	153	154	147
Overall Study Lost to Follow-up	6	3	8
Overall Study Physician Decision	1	0	1
Overall Study Protocol Violation	0	0	1
Overall Study Withdrawal by Subject	32	14	12

Baseline Characteristics

Study to Evaluate the Safety and Efficacy of Two Different Dosing Schedules of Pembrolizumab (MK-3475) Compared to Ipilimumab in Participants With Advanced Melanoma (MK-3475-006/KEYNOTE-006)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ipilimumab n=278 Participants Participants received ipilimumab, 3 mg/kg intravenously (IV), once every 3 weeks (Q3W) for a total of 4 doses (up to approximately 3 months).	Pembrolizumab Q2W n=279 Participants Participants received pembrolizumab, 10 mg/kg IV, once every 2 weeks (Q2W) for up to approximately 24 months.	Pembrolizumab Q3W n=277 Participants Participants received pembrolizumab, 10 mg/kg IV, Q3W for up to approximately 24 months.	Total n=834 Participants Total of all reporting groups
Age, Continuous	59.9 Years STANDARD_DEVIATION 14.2 • n=5 Participants	59.9 Years STANDARD_DEVIATION 14.6 • n=7 Participants	61.2 Years STANDARD_DEVIATION 13.6 • n=5 Participants	60.3 Years STANDARD_DEVIATION 14.1 • n=4 Participants
Sex: Female, Male Female	116 Participants n=5 Participants	118 Participants n=7 Participants	103 Participants n=5 Participants	337 Participants n=4 Participants
Sex: Female, Male Male	162 Participants n=5 Participants	161 Participants n=7 Participants	174 Participants n=5 Participants	497 Participants n=4 Participants

PRIMARY outcome

Timeframe: Up to approximately 12 months (through first pre-specified statistical analysis cut-off date of 03-Sep-2014)

Population: The ITT population, comprising all participants as randomized to a study arm.

Outcome measures

Outcome measures
Measure	Ipilimumab n=278 Participants Participants received ipilimumab, 3 mg/kg intravenously (IV), once every 3 weeks (Q3W) for a total of 4 doses (up to approximately 3 months).	Pembrolizumab Q2W n=279 Participants Participants received pembrolizumab, 10 mg/kg IV, once every 2 weeks (Q2W) for up to approximately 24 months.	Pembrolizumab Q3W n=277 Participants Participants received pembrolizumab, 10 mg/kg IV, Q3W for up to approximately 24 months.
Progression-free Survival (PFS) According to Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Independent Radiology Plus Oncology Review (IRO)	2.8 Months Interval 2.8 to 2.9	5.5 Months Interval 3.4 to 6.9	4.1 Months Interval 2.9 to 6.9

PRIMARY outcome

Timeframe: Month 12

Population: The ITT population, comprising all participants as randomized to a study arm.

OS was defined as the time from randomization to death due to any cause. The percentage of participants with OS (OS rate) at 12 months was reported for each arm. The reported percentage was estimated using a product-limit (Kaplan-Meier) method for censored data; data were censored at the date of cut-off. The primary analysis of OS was performed at the time of the second protocol pre-specified statistical analysis, with data cut-off of 03-Mar-2015.

Outcome measures

Outcome measures
Measure	Ipilimumab n=278 Participants Participants received ipilimumab, 3 mg/kg intravenously (IV), once every 3 weeks (Q3W) for a total of 4 doses (up to approximately 3 months).	Pembrolizumab Q2W n=279 Participants Participants received pembrolizumab, 10 mg/kg IV, once every 2 weeks (Q2W) for up to approximately 24 months.	Pembrolizumab Q3W n=277 Participants Participants received pembrolizumab, 10 mg/kg IV, Q3W for up to approximately 24 months.
Percentage of Participants With Overall Survival (OS) at 12 Months	58.2 Percentage of participants Interval 51.8 to 64.0	74.1 Percentage of participants Interval 68.5 to 78.9	68.4 Percentage of participants Interval 62.5 to 73.6

SECONDARY outcome

Timeframe: Up to approximately 12 months (through first pre-specified statistical analysis cut-off date of 03-Sep-2014)

Population: The ITT population, comprising all participants as randomized to a study arm.

ORR was defined as the percentage of the participants with a best tumor response of complete response (CR: disappearance of all target lesions with any pathological lymph nodes having a reduction in short axis to \<10 mm) or partial response (PR: ≥30% decrease in the sum of diameters of target lesions), based on IRO using RECIST 1.1. The primary analysis of ORR was performed at the time of the first protocol pre-specified statistical analysis, with data cut-off of 03-Sep-2014.

Outcome measures

Outcome measures
Measure	Ipilimumab n=278 Participants Participants received ipilimumab, 3 mg/kg intravenously (IV), once every 3 weeks (Q3W) for a total of 4 doses (up to approximately 3 months).	Pembrolizumab Q2W n=279 Participants Participants received pembrolizumab, 10 mg/kg IV, once every 2 weeks (Q2W) for up to approximately 24 months.	Pembrolizumab Q3W n=277 Participants Participants received pembrolizumab, 10 mg/kg IV, Q3W for up to approximately 24 months.
Objective Response Rate (ORR) According to RECIST 1.1 as Assessed by IRO	11.9 Percentage of Participants Interval 8.3 to 16.3	33.7 Percentage of Participants Interval 28.2 to 39.6	32.9 Percentage of Participants Interval 27.4 to 38.7

Adverse Events

Ipilimumab

Serious events: 77 serious events

Other events: 220 other events

Deaths: 173 deaths

Pembrolizumab Q2W

Serious events: 89 serious events

Other events: 257 other events

Deaths: 166 deaths

Pembrolizumab Q3W

Serious events: 90 serious events

Other events: 247 other events

Deaths: 162 deaths

Serious adverse events

Other adverse events

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp.

Phone: 1-800-672-6372

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Sponsor must have the opportunity to review all proposed abstracts, manuscripts, or presentations regarding this study 60 days prior to submission for publication/presentation.
Publication restrictions are in place

Restriction type: OTHER

Serious adverse events
Measure	Ipilimumab n=256 participants at risk Participants received ipilimumab, 3 mg/kg intravenously (IV), once every 3 weeks (Q3W) for a total of 4 doses (up to approximately 3 months).	Pembrolizumab Q2W n=278 participants at risk Participants received pembrolizumab, 10 mg/kg IV, once every 2 weeks (Q2W) for up to approximately 24 months.	Pembrolizumab Q3W n=277 participants at risk Participants received pembrolizumab, 10 mg/kg IV, Q3W for up to approximately 24 months.
General disorders Fatigue aggravated	0.00% 0/256 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	0.00% 0/278 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	0.36% 1/277 • Number of events 1 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
General disorders Fever	1.6% 4/256 • Number of events 4 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	0.36% 1/278 • Number of events 1 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	0.00% 0/277 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
General disorders General body pain	0.39% 1/256 • Number of events 1 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	0.00% 0/278 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	0.00% 0/277 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Blood and lymphatic system disorders Anaemia	0.00% 0/256 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	0.72% 2/278 • Number of events 2 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	0.72% 2/277 • Number of events 2 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Blood and lymphatic system disorders Anaemia aggravated	0.00% 0/256 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	0.00% 0/278 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	1.1% 3/277 • Number of events 3 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Blood and lymphatic system disorders Lymph nodes enlarged	0.00% 0/256 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	0.36% 1/278 • Number of events 1 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	0.00% 0/277 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/256 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	0.00% 0/278 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	0.72% 2/277 • Number of events 2 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Cardiac disorders Acute coronary syndrome	0.00% 0/256 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	0.00% 0/278 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	0.36% 1/277 • Number of events 1 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Cardiac disorders Angina unstable	0.00% 0/256 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	0.00% 0/278 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	0.36% 1/277 • Number of events 1 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Cardiac disorders Atrial fibrillation	0.00% 0/256 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	0.36% 1/278 • Number of events 1 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	0.00% 0/277 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Cardiac disorders Atrial flutter	0.39% 1/256 • Number of events 1 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	0.00% 0/278 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	0.00% 0/277 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Cardiac disorders Cardiac failure congestive	0.00% 0/256 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	0.00% 0/278 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	0.36% 1/277 • Number of events 1 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Cardiac disorders Congestive cardiac failure aggravated	0.00% 0/256 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	0.00% 0/278 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	0.36% 1/277 • Number of events 2 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Cardiac disorders Decompensation cardiac	0.00% 0/256 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	0.36% 1/278 • Number of events 1 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	0.72% 2/277 • Number of events 2 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Cardiac disorders Heart attack	0.00% 0/256 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	0.36% 1/278 • Number of events 1 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	0.00% 0/277 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Cardiac disorders Paroxysmal atrial fibrillation	0.00% 0/256 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	0.00% 0/278 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	0.36% 1/277 • Number of events 1 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Cardiac disorders Pericardial effusion	0.00% 0/256 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	0.36% 1/278 • Number of events 1 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	0.00% 0/277 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Congenital, familial and genetic disorders Pyloric stenosis	0.00% 0/256 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	0.00% 0/278 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	0.36% 1/277 • Number of events 1 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Ear and labyrinth disorders Hearing impaired	0.00% 0/256 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	0.36% 1/278 • Number of events 1 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	0.00% 0/277 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Endocrine disorders Adrenal insufficiency	0.39% 1/256 • Number of events 1 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	0.72% 2/278 • Number of events 2 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	0.00% 0/277 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Endocrine disorders Adrenomegaly	0.00% 0/256 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	0.36% 1/278 • Number of events 1 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	0.00% 0/277 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Endocrine disorders Hypophysitis	0.78% 2/256 • Number of events 2 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	0.36% 1/278 • Number of events 1 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	0.36% 1/277 • Number of events 1 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Endocrine disorders Hypopituitarism	0.39% 1/256 • Number of events 1 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	0.36% 1/278 • Number of events 1 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	0.00% 0/277 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Endocrine disorders Hypothyroidism	0.00% 0/256 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	0.36% 1/278 • Number of events 1 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	0.00% 0/277 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Endocrine disorders Panhypopituitarism	0.39% 1/256 • Number of events 1 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	0.00% 0/278 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	0.00% 0/277 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Eye disorders Diplopia	0.39% 1/256 • Number of events 1 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	0.00% 0/278 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	0.00% 0/277 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Eye disorders Neovascular glaucoma	0.00% 0/256 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	0.36% 1/278 • Number of events 1 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	0.00% 0/277 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Eye disorders Papilloedema	0.00% 0/256 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	0.00% 0/278 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	0.36% 1/277 • Number of events 1 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Gastrointestinal disorders Abdominal distension	0.00% 0/256 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	0.36% 1/278 • Number of events 1 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	0.00% 0/277 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Gastrointestinal disorders Abdominal pain	0.78% 2/256 • Number of events 2 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	0.36% 1/278 • Number of events 1 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	0.72% 2/277 • Number of events 2 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Gastrointestinal disorders Abdominal pain lower	0.00% 0/256 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	0.36% 1/278 • Number of events 1 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	0.00% 0/277 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Gastrointestinal disorders Anal fistula	0.00% 0/256 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	0.36% 1/278 • Number of events 1 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	0.00% 0/277 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Gastrointestinal disorders Autoimmune colitis	0.00% 0/256 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	0.36% 1/278 • Number of events 1 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	0.00% 0/277 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Gastrointestinal disorders Autoimmune pancreatitis	0.00% 0/256 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	0.36% 1/278 • Number of events 1 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	0.00% 0/277 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Gastrointestinal disorders Blood in stool	0.00% 0/256 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	0.00% 0/278 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	0.36% 1/277 • Number of events 1 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Gastrointestinal disorders Colitis	6.2% 16/256 • Number of events 18 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	2.2% 6/278 • Number of events 6 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	2.2% 6/277 • Number of events 6 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Gastrointestinal disorders Constipation	0.39% 1/256 • Number of events 1 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	0.00% 0/278 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	0.36% 1/277 • Number of events 1 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Gastrointestinal disorders Diarrhoea	3.5% 9/256 • Number of events 9 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	2.5% 7/278 • Number of events 7 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	1.1% 3/277 • Number of events 3 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Gastrointestinal disorders Enteritis	0.39% 1/256 • Number of events 1 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	0.00% 0/278 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	0.00% 0/277 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Gastrointestinal disorders Enterocolitis	0.78% 2/256 • Number of events 2 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	0.00% 0/278 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	0.00% 0/277 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.

Other adverse events
Measure	Ipilimumab n=256 participants at risk Participants received ipilimumab, 3 mg/kg intravenously (IV), once every 3 weeks (Q3W) for a total of 4 doses (up to approximately 3 months).	Pembrolizumab Q2W n=278 participants at risk Participants received pembrolizumab, 10 mg/kg IV, once every 2 weeks (Q2W) for up to approximately 24 months.	Pembrolizumab Q3W n=277 participants at risk Participants received pembrolizumab, 10 mg/kg IV, Q3W for up to approximately 24 months.
Blood and lymphatic system disorders Anaemia	4.7% 12/256 • Number of events 14 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	12.2% 34/278 • Number of events 44 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	8.3% 23/277 • Number of events 28 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Endocrine disorders Hyperthyroidism	2.3% 6/256 • Number of events 6 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	6.1% 17/278 • Number of events 19 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	4.3% 12/277 • Number of events 12 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Endocrine disorders Hypothyroidism	2.0% 5/256 • Number of events 5 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	10.4% 29/278 • Number of events 31 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	9.0% 25/277 • Number of events 26 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Gastrointestinal disorders Abdominal pain	6.2% 16/256 • Number of events 19 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	10.4% 29/278 • Number of events 37 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	6.5% 18/277 • Number of events 19 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Gastrointestinal disorders Constipation	11.3% 29/256 • Number of events 32 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	19.1% 53/278 • Number of events 78 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	14.1% 39/277 • Number of events 47 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Gastrointestinal disorders Diarrhoea	27.0% 69/256 • Number of events 91 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	29.5% 82/278 • Number of events 162 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	27.4% 76/277 • Number of events 116 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Gastrointestinal disorders Dry mouth	0.39% 1/256 • Number of events 1 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	9.4% 26/278 • Number of events 27 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	7.2% 20/277 • Number of events 21 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Gastrointestinal disorders Nausea	21.5% 55/256 • Number of events 66 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	26.3% 73/278 • Number of events 90 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	25.3% 70/277 • Number of events 88 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Gastrointestinal disorders Vomiting	12.1% 31/256 • Number of events 35 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	16.2% 45/278 • Number of events 66 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	9.7% 27/277 • Number of events 32 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
General disorders Asthenia	10.2% 26/256 • Number of events 29 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	16.2% 45/278 • Number of events 92 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	14.8% 41/277 • Number of events 56 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
General disorders Fatigue	28.5% 73/256 • Number of events 78 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	32.4% 90/278 • Number of events 125 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	30.7% 85/277 • Number of events 116 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
General disorders Fever	7.8% 20/256 • Number of events 22 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	10.4% 29/278 • Number of events 40 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	7.6% 21/277 • Number of events 35 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
General disorders Flu-like symptoms	3.1% 8/256 • Number of events 9 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	7.6% 21/278 • Number of events 23 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	5.1% 14/277 • Number of events 27 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Infections and infestations Common cold syndrome	3.5% 9/256 • Number of events 9 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	7.6% 21/278 • Number of events 32 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	5.4% 15/277 • Number of events 18 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Infections and infestations Upper respiratory tract infection	4.3% 11/256 • Number of events 11 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	11.2% 31/278 • Number of events 43 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	7.6% 21/277 • Number of events 25 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Infections and infestations Urinary tract infection	3.9% 10/256 • Number of events 11 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	7.9% 22/278 • Number of events 33 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	5.1% 14/277 • Number of events 19 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Investigations Alanine aminotransferase increased	4.7% 12/256 • Number of events 13 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	7.6% 21/278 • Number of events 32 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	5.8% 16/277 • Number of events 19 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Investigations Aspartate aminotransferase increased	4.7% 12/256 • Number of events 13 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	7.9% 22/278 • Number of events 35 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	4.3% 12/277 • Number of events 17 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Investigations Lactate dehydrogenase increased	2.3% 6/256 • Number of events 6 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	5.0% 14/278 • Number of events 25 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	2.2% 6/277 • Number of events 11 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Investigations Weight decreased	5.1% 13/256 • Number of events 13 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	7.2% 20/278 • Number of events 21 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	9.4% 26/277 • Number of events 28 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Metabolism and nutrition disorders Anorexia	9.4% 24/256 • Number of events 27 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	11.2% 31/278 • Number of events 39 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	12.6% 35/277 • Number of events 36 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Metabolism and nutrition disorders Hypokalaemia	2.0% 5/256 • Number of events 7 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	5.8% 16/278 • Number of events 34 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	4.7% 13/277 • Number of events 14 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Musculoskeletal and connective tissue disorders Arthralgia	7.0% 18/256 • Number of events 18 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	14.7% 41/278 • Number of events 63 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	14.1% 39/277 • Number of events 42 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Musculoskeletal and connective tissue disorders Back pain	3.1% 8/256 • Number of events 8 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	10.4% 29/278 • Number of events 32 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	4.0% 11/277 • Number of events 12 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Musculoskeletal and connective tissue disorders Knee pain	2.3% 6/256 • Number of events 6 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	5.4% 15/278 • Number of events 21 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	2.9% 8/277 • Number of events 8 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Musculoskeletal and connective tissue disorders Low back pain	2.0% 5/256 • Number of events 5 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	6.1% 17/278 • Number of events 19 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	4.3% 12/277 • Number of events 14 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Musculoskeletal and connective tissue disorders Myalgia	3.1% 8/256 • Number of events 8 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	11.5% 32/278 • Number of events 38 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	5.4% 15/277 • Number of events 18 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Musculoskeletal and connective tissue disorders Shoulder pain	3.1% 8/256 • Number of events 9 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	7.6% 21/278 • Number of events 26 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	4.3% 12/277 • Number of events 12 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Nervous system disorders Dizziness	3.5% 9/256 • Number of events 9 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	9.7% 27/278 • Number of events 34 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	7.9% 22/277 • Number of events 26 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Nervous system disorders Headache	10.5% 27/256 • Number of events 29 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	16.2% 45/278 • Number of events 72 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	11.9% 33/277 • Number of events 58 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Psychiatric disorders Anxiety	1.6% 4/256 • Number of events 4 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	5.0% 14/278 • Number of events 14 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	3.6% 10/277 • Number of events 10 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Psychiatric disorders Insomnia	5.5% 14/256 • Number of events 14 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	10.1% 28/278 • Number of events 33 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	7.2% 20/277 • Number of events 20 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Respiratory, thoracic and mediastinal disorders Cough	6.2% 16/256 • Number of events 17 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	20.9% 58/278 • Number of events 75 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	15.5% 43/277 • Number of events 48 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Respiratory, thoracic and mediastinal disorders Dry cough	0.78% 2/256 • Number of events 2 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	3.2% 9/278 • Number of events 10 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	5.4% 15/277 • Number of events 16 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Respiratory, thoracic and mediastinal disorders Dyspnoea	5.9% 15/256 • Number of events 16 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	10.8% 30/278 • Number of events 32 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	9.7% 27/277 • Number of events 27 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Respiratory, thoracic and mediastinal disorders Sore throat	1.6% 4/256 • Number of events 5 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	5.8% 16/278 • Number of events 16 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	1.8% 5/277 • Number of events 5 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Skin and subcutaneous tissue disorders Dry skin	2.3% 6/256 • Number of events 6 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	6.8% 19/278 • Number of events 20 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	6.1% 17/277 • Number of events 17 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Skin and subcutaneous tissue disorders Pruritus	25.4% 65/256 • Number of events 76 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	24.5% 68/278 • Number of events 99 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	21.3% 59/277 • Number of events 83 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Skin and subcutaneous tissue disorders Rash	10.9% 28/256 • Number of events 29 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	13.3% 37/278 • Number of events 55 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	13.0% 36/277 • Number of events 51 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Skin and subcutaneous tissue disorders Rash maculo-papular	3.1% 8/256 • Number of events 8 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	6.1% 17/278 • Number of events 23 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.	3.6% 10/277 • Number of events 15 • Up to approximately 69 months (through End of Trial Analysis data cut-off date of 03-Jun-2019) All-Cause Mortality table includes all randomized participants. Serious and Other adverse events (AEs) tables include all randomized participants who received at least 1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.