Trial Outcomes & Findings for Study of Pembrolizumab (MK-3475) in Participants With Relapsed or Refractory Primary Mediastinal Large B-cell Lymphoma or Relapsed or Refractory Richter Syndrome (MK-3475-170/KEYNOTE-170) (NCT NCT02576990)

Last Updated: 2023-07-27

Results Overview

The ORR was assessed by independent central review utilizing the International Working Group \[IWG\] response assessment criteria per Cheson 2007 of pembrolizumab in participants with rrPMBCL. For participants with rrRS, IWG criteria with special considerations for RS was used for progression. The ORR was defined as the percentage of participants who had a response (complete response, CR or partial response, PR) prior to disease progression. CR is the disappearance of all evidence of disease and PR is the regression of measurable disease and no new sites. Participants with missing data were considered non-responders. In the rrPMBCL cohort, an exact binomial test was conducted versus a fixed historical control rate. For the rrPMBCL cohort, the ORR was estimated as well as a 95% 2-sided exact confidence interval (CI) using the Clopper-Pearson method whereas the rrRS cohort was estimated with a 90% 2-sided CI.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

80 participants

Primary outcome timeframe

Up to approximately 27 months (Database Cutoff: 28MAY2019)

Results posted on

2023-07-27

Participant Flow

Of the 80 participants allocated in the study, 76 participants received at least one dose of study treatment.

Participant milestones

Participant milestones
Measure	Pembrolizumab: Relapsed or Refractory Primary Mediastinal Large B-cell Lymphoma (rrPMBCL) Pembrolizumab 200 mg every 3 weeks (Q3W), intravenous infusion (IV) on Day 1 of each 3-week cycle for up to 35 administrations (approximately 2 years).	Pembrolizumab: Relapsed or Refractory Richter Syndrome (rrRS) Pembrolizumab 200 mg Q3W, IV on Day 1 of each 3-week cycle for up to 35 administrations (approximately 2 years).
Overall Study STARTED	56	24
Overall Study Treated	53	23
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	56	24

Reasons for withdrawal

Reasons for withdrawal
Measure	Pembrolizumab: Relapsed or Refractory Primary Mediastinal Large B-cell Lymphoma (rrPMBCL) Pembrolizumab 200 mg every 3 weeks (Q3W), intravenous infusion (IV) on Day 1 of each 3-week cycle for up to 35 administrations (approximately 2 years).	Pembrolizumab: Relapsed or Refractory Richter Syndrome (rrRS) Pembrolizumab 200 mg Q3W, IV on Day 1 of each 3-week cycle for up to 35 administrations (approximately 2 years).
Overall Study Death	29	18
Overall Study Physician Decision	1	0
Overall Study Screen failure	2	0
Overall Study Sponsor's decision	24	4
Overall Study Withdrawal by Subject	0	2

Baseline Characteristics

Study of Pembrolizumab (MK-3475) in Participants With Relapsed or Refractory Primary Mediastinal Large B-cell Lymphoma or Relapsed or Refractory Richter Syndrome (MK-3475-170/KEYNOTE-170)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Pembrolizumab: Relapsed or Refractory Primary Mediastinal Large B-cell Lymphoma (rrPMBCL) n=56 Participants Pembrolizumab 200 mg every 3 weeks (Q3W), intravenous infusion (IV) on Day 1 of each 3-week cycle for up to 35 administrations (approximately 2 years).	Pembrolizumab: Relapsed or Refractory Richter Syndrome (rrRS) n=24 Participants Pembrolizumab 200 mg Q3W, IV on Day 1 of each 3-week cycle for up to 35 administrations (approximately 2 years).	Total n=80 Participants Total of all reporting groups
Age, Continuous	35.0 Years STANDARD_DEVIATION 10.4 • n=5 Participants	67.2 Years STANDARD_DEVIATION 11.0 • n=7 Participants	44.7 Years STANDARD_DEVIATION 18.2 • n=5 Participants
Sex: Female, Male Female	30 Participants n=5 Participants	7 Participants n=7 Participants	37 Participants n=5 Participants
Sex: Female, Male Male	26 Participants n=5 Participants	17 Participants n=7 Participants	43 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=5 Participants	1 Participants n=7 Participants	5 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	37 Participants n=5 Participants	21 Participants n=7 Participants	58 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	15 Participants n=5 Participants	2 Participants n=7 Participants	17 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) White	51 Participants n=5 Participants	24 Participants n=7 Participants	75 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	4 Participants n=5 Participants	0 Participants n=7 Participants	4 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to approximately 27 months (Database Cutoff: 28MAY2019)

Population: The analysis population included all participants who received at least one dose of study medication (pembrolizumab).

Outcome measures

Outcome measures
Measure	Pembrolizumab: Relapsed or Refractory Primary Mediastinal Large B-cell Lymphoma (rrPMBCL) n=53 Participants Pembrolizumab 200 mg every 3 weeks (Q3W), intravenous infusion (IV) on Day 1 of each 3-week cycle for up to 35 administrations (approximately 2 years).	Pembrolizumab: Relapsed or Refractory Richter Syndrome (rrRS) n=23 Participants Pembrolizumab 200 mg Q3W, IV on Day 1 of each 3-week cycle for up to 35 administrations (approximately 2 years).
Objective Response Rate (ORR) Based on International Working Group (IWG) Response Assessment Criteria Per Independent Central Review	45.3 Percentage of participants Interval 31.6 to 59.6	13.0 Percentage of participants Interval 3.7 to 30.4

SECONDARY outcome

Timeframe: Up to approximately 27 months (Database Cutoff Date: 28MAY2019)

Population: The analysis population included all participants who received at least one dose of study medication (pembrolizumab).

The ORR was assessed by Investigator assessment utilizing the IWG response assessment criteria per Cheson 2007 of pembrolizumab in participants with rrPMBCL. For participants with rrRS, IWG criteria with special considerations for RS was used for progression. The ORR was defined as the percentage of participants who had a response (CR or PR) prior to disease progression. CR is the disappearance of all evidence of disease and PR is the regression of measurable disease and no new sites. Participants with missing data were considered non-responders. In the rrPMBCL cohort, an exact binomial test was conducted versus a fixed historical control rate.

Outcome measures

Outcome measures
Measure	Pembrolizumab: Relapsed or Refractory Primary Mediastinal Large B-cell Lymphoma (rrPMBCL) n=53 Participants Pembrolizumab 200 mg every 3 weeks (Q3W), intravenous infusion (IV) on Day 1 of each 3-week cycle for up to 35 administrations (approximately 2 years).	Pembrolizumab: Relapsed or Refractory Richter Syndrome (rrRS) n=23 Participants Pembrolizumab 200 mg Q3W, IV on Day 1 of each 3-week cycle for up to 35 administrations (approximately 2 years).
ORR Based on IWG Response Assessment Criteria by Investigator Assessment	41.5 Percentage of participants Interval 30.0 to 53.7	4.3 Percentage of participants Interval 0.2 to 19.0

SECONDARY outcome

Timeframe: Up to approximately 27 months (Database Cutoff Date: 28MAY2019)

Population: The analysis population included all participants who received at least one dose of study medication (pembrolizumab).

PFS was defined as the time from first dose to the first documented progressive disease (PD) or death due to any cause, whichever occurs first. PD is the appearance of any new lesion or increase by ≥ 50% of previously involved site from nadir. Calculated from the product-limit (Kaplan-Meier) method for censored data.

Outcome measures

Outcome measures
Measure	Pembrolizumab: Relapsed or Refractory Primary Mediastinal Large B-cell Lymphoma (rrPMBCL) n=53 Participants Pembrolizumab 200 mg every 3 weeks (Q3W), intravenous infusion (IV) on Day 1 of each 3-week cycle for up to 35 administrations (approximately 2 years).	Pembrolizumab: Relapsed or Refractory Richter Syndrome (rrRS) n=23 Participants Pembrolizumab 200 mg Q3W, IV on Day 1 of each 3-week cycle for up to 35 administrations (approximately 2 years).
Progression Free Survival (PFS) Based on IWG Response Assessment Criteria by Independent Central Review	5.5 Months Interval 2.8 to 15.1	1.6 Months Interval 1.0 to 2.1

SECONDARY outcome

Timeframe: Up to approximately 27 months (Database Cutoff Date: 28MAY2019)

Population: The analysis population included all participants who received at least one dose of study medication (pembrolizumab).

PFS was defined as the time from the first dose to the first documented PD or death due to any cause, whichever occurs first. PD is the appearance of any new lesion or increase by ≥ 50% of previously involved site from nadir. Calculated from the product-limit (Kaplan-Meier) method for censored data.

Outcome measures

Outcome measures
Measure	Pembrolizumab: Relapsed or Refractory Primary Mediastinal Large B-cell Lymphoma (rrPMBCL) n=53 Participants Pembrolizumab 200 mg every 3 weeks (Q3W), intravenous infusion (IV) on Day 1 of each 3-week cycle for up to 35 administrations (approximately 2 years).	Pembrolizumab: Relapsed or Refractory Richter Syndrome (rrRS) n=23 Participants Pembrolizumab 200 mg Q3W, IV on Day 1 of each 3-week cycle for up to 35 administrations (approximately 2 years).
Progression Free Survival (PFS) Based on IWG Response Assessment Criteria by Investigator Assessment	4.3 Months Interval 2.8 to 13.8	1.8 Months Interval 1.0 to 2.1

SECONDARY outcome

Timeframe: Up to approximately 27 months (Database Cutoff Date: 28MAY2019)

Population: The analysis population included all participants who received at least one dose of study medication (pembrolizumab) and who achieved a CR or PR by independent central review, as the time from start of the first documentation of objective tumor response (CR or PR).

The DOR was defined, only for the subgroup of participants who achieved a CR or PR by independent central review, as the time from start of the first documentation of objective tumor response (CR or PR) to the first documentation of PD or to death due to any cause, whichever comes first. CR is the disappearance of all evidence of disease and PR is the regression of measurable disease and no new sites. PD is the appearance any new lesion or increase by ≥ 50% of previously involved site from nadir. The analysis consisted of Kaplan-Meier estimates. DOR data was censored on the date of the last disease assessment documenting absence of PD for participants who did not have tumor progression and were still on study at the time of an analysis, were given antitumor treatment other than the study treatment, or were removed from study prior to documentation of tumor progression.

Outcome measures

Outcome measures
Measure	Pembrolizumab: Relapsed or Refractory Primary Mediastinal Large B-cell Lymphoma (rrPMBCL) n=24 Participants Pembrolizumab 200 mg every 3 weeks (Q3W), intravenous infusion (IV) on Day 1 of each 3-week cycle for up to 35 administrations (approximately 2 years).	Pembrolizumab: Relapsed or Refractory Richter Syndrome (rrRS) n=3 Participants Pembrolizumab 200 mg Q3W, IV on Day 1 of each 3-week cycle for up to 35 administrations (approximately 2 years).
Duration of Response (DOR) Based on IWG Response Assessment Criteria by Independent Central Review in Participants With Responses	NA Months Interval 25.2 to NA = Median DOR was not reached (no progressive disease by time of last disease assessment). NA = DOR upper limit was not reached (no progressive disease by time of last disease assessment).	4.5 Months Interval 2.7 to 6.2

SECONDARY outcome

Timeframe: Up to approximately 27 months (Database Cutoff Date: 28MAY2019)

Population: The analysis population included all participants who received at least one dose of study medication (pembrolizumab) and who achieved a CR or PR by investigator assessment, as the time from start of the first documentation of objective tumor response (CR or PR).

The DOR was defined, only for the subgroup of participants who achieved a CR or PR by investigator assessment, as the time from start of the first documentation of objective tumor response (CR or PR) to the first documentation of PD or to death due to any cause, whichever comes first. CR is the disappearance of all evidence of disease and PR is the regression of measurable disease and no new sites. PD is the appearance any new lesion or increase by ≥ 50% of previously involved site from nadir. The analysis consisted of Kaplan-Meier estimates. DOR data was censored on the date of the last disease assessment documenting absence of PD for participants who did not have tumor progression and were still on study at the time of an analysis, were given antitumor treatment other than the study treatment, or were removed from study prior to documentation of tumor progression.

Outcome measures

Outcome measures
Measure	Pembrolizumab: Relapsed or Refractory Primary Mediastinal Large B-cell Lymphoma (rrPMBCL) n=24 Participants Pembrolizumab 200 mg every 3 weeks (Q3W), intravenous infusion (IV) on Day 1 of each 3-week cycle for up to 35 administrations (approximately 2 years).	Pembrolizumab: Relapsed or Refractory Richter Syndrome (rrRS) n=1 Participants Pembrolizumab 200 mg Q3W, IV on Day 1 of each 3-week cycle for up to 35 administrations (approximately 2 years).
Duration of Response (DOR) Based on IWG Response Assessment Criteria by Investigator Assessment in Participants With Responses	NA Months Interval 25.2 to NA = Median DOR was not reached (no progressive disease by time of last disease assessment). NA = DOR upper limit was not reached (no progressive disease by time of last disease assessment).	NA Months NA = Median DOR was not reached (no progressive disease by time of last disease assessment). NA = DOR upper and lower limits were not reached (no progressive disease by time of last disease assessment).

SECONDARY outcome

Timeframe: Up to approximately 27 months (Database Cutoff Date: 28MAY2019)

Population: The analysis population included all participants who received at least one dose of study medication (pembrolizumab).

The DCR was defined as the percentage of participants in the analysis population who have achieved a CR, PR or stable disease (SD) response prior to PD. CR is the disappearance of all evidence of disease and PR is the regression of measurable disease and no new sites. SD is the failure to attain CR/PR or PD. PD is the appearance any new lesion or increase by ≥ 50% of previously involved site from nadir. Participants with missing data were considered non-responders.

Outcome measures

Outcome measures
Measure	Pembrolizumab: Relapsed or Refractory Primary Mediastinal Large B-cell Lymphoma (rrPMBCL) n=53 Participants Pembrolizumab 200 mg every 3 weeks (Q3W), intravenous infusion (IV) on Day 1 of each 3-week cycle for up to 35 administrations (approximately 2 years).	Pembrolizumab: Relapsed or Refractory Richter Syndrome (rrRS) n=23 Participants Pembrolizumab 200 mg Q3W, IV on Day 1 of each 3-week cycle for up to 35 administrations (approximately 2 years).
Disease Control Rate (DCR) Based on IWG Response Assessment Criteria by Independent Central Review	54.7 Percentage of participants Interval 42.6 to 66.5	17.4 Percentage of participants Interval 6.2 to 35.5

SECONDARY outcome

Timeframe: Up to approximately 27 months (Database Cutoff Date: 28MAY2019)

Population: The analysis population included all participants who received at least one dose of study medication (pembrolizumab).

The DCR was defined as the percentage of participants in the analysis population who have achieved a CR, PR or SD response prior to PD. CR is the disappearance of all evidence of disease and PR is the regression of measurable disease and no new sites. SD is the failure to attain CR/PR or PD. PD is the appearance any new lesion or increase by ≥ 50% of previously involved site from nadir. Participants with missing data were considered non-responders.

Outcome measures

Outcome measures
Measure	Pembrolizumab: Relapsed or Refractory Primary Mediastinal Large B-cell Lymphoma (rrPMBCL) n=53 Participants Pembrolizumab 200 mg every 3 weeks (Q3W), intravenous infusion (IV) on Day 1 of each 3-week cycle for up to 35 administrations (approximately 2 years).	Pembrolizumab: Relapsed or Refractory Richter Syndrome (rrRS) n=23 Participants Pembrolizumab 200 mg Q3W, IV on Day 1 of each 3-week cycle for up to 35 administrations (approximately 2 years).
Disease Control Rate (DCR) Based on IWG Response Assessment Criteria by Investigator Assessment	52.8 Percentage of participants Interval 40.7 to 64.7	26.1 Percentage of participants Interval 12.0 to 45.1

SECONDARY outcome

Timeframe: Up to approximately 27 months (Database Cutoff Date: 28MAY2019)

Population: The analysis population included all participants who received at least one dose of study medication (pembrolizumab).

OS was defined as the time from the first dose to death due to any cause. OS is presented from product limit (Kaplan-Meier) method for censored data (censored at the last assessment).

Outcome measures

Outcome measures
Measure	Pembrolizumab: Relapsed or Refractory Primary Mediastinal Large B-cell Lymphoma (rrPMBCL) n=53 Participants Pembrolizumab 200 mg every 3 weeks (Q3W), intravenous infusion (IV) on Day 1 of each 3-week cycle for up to 35 administrations (approximately 2 years).	Pembrolizumab: Relapsed or Refractory Richter Syndrome (rrRS) n=23 Participants Pembrolizumab 200 mg Q3W, IV on Day 1 of each 3-week cycle for up to 35 administrations (approximately 2 years).
Overall Survival (OS)	22.3 Months Interval 7.3 to NA = OS upper limit was not reached (insufficient number of deaths by time of last disease assessment).	3.8 Months Interval 1.8 to 18.1

SECONDARY outcome

Timeframe: Up to approximately 30 months (Up to 90 days after last dose of study treatment) (Database Cutoff Date: 28MAY2019)

Population: The analysis population included all participants who received at least one dose of study medication (pembrolizumab).

An adverse event (AE) is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study. The number of participants who experienced an AE were reported.

Outcome measures

Outcome measures
Measure	Pembrolizumab: Relapsed or Refractory Primary Mediastinal Large B-cell Lymphoma (rrPMBCL) n=53 Participants Pembrolizumab 200 mg every 3 weeks (Q3W), intravenous infusion (IV) on Day 1 of each 3-week cycle for up to 35 administrations (approximately 2 years).	Pembrolizumab: Relapsed or Refractory Richter Syndrome (rrRS) n=23 Participants Pembrolizumab 200 mg Q3W, IV on Day 1 of each 3-week cycle for up to 35 administrations (approximately 2 years).
Number of Participants Who Experienced an Adverse Event (AE)	50 Participants	23 Participants

SECONDARY outcome

Timeframe: Up to approximately 27 months (Database Cutoff Date: 28MAY2019)

Population: The analysis population included all participants who received at least one dose of study medication (pembrolizumab).

An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study. The number of participants who discontinued study drug due to an AE were reported.

Outcome measures

Outcome measures
Measure	Pembrolizumab: Relapsed or Refractory Primary Mediastinal Large B-cell Lymphoma (rrPMBCL) n=53 Participants Pembrolizumab 200 mg every 3 weeks (Q3W), intravenous infusion (IV) on Day 1 of each 3-week cycle for up to 35 administrations (approximately 2 years).	Pembrolizumab: Relapsed or Refractory Richter Syndrome (rrRS) n=23 Participants Pembrolizumab 200 mg Q3W, IV on Day 1 of each 3-week cycle for up to 35 administrations (approximately 2 years).
Number of Participants Who Discontinued Study Drug Due to an AE	6 Participants	4 Participants

Adverse Events

Pembrolizumab: Relapsed or Refractory Primary Mediastinal Large B-cell Lymphoma (rrPMBCL)

Serious events: 14 serious events

Other events: 46 other events

Deaths: 30 deaths

Pembrolizumab: Relapsed or Refractory Richter Syndrome (rrRS)

Serious events: 15 serious events

Other events: 23 other events

Deaths: 19 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 trial 45 days prior to submission for publication/presentation. Any information identified by the Sponsor as confidential must be deleted prior to submission; this confidentiality does not include efficacy and safety results. Sponsor review can be expedited to meet publication timelines.
Publication restrictions are in place

Restriction type: OTHER

Serious adverse events
Measure	Pembrolizumab: Relapsed or Refractory Primary Mediastinal Large B-cell Lymphoma (rrPMBCL) n=53 participants at risk Pembrolizumab 200 mg every 3 weeks (Q3W), intravenous infusion (IV) on Day 1 of each 3-week cycle for up to 35 administrations (approximately 2 years).	Pembrolizumab: Relapsed or Refractory Richter Syndrome (rrRS) n=23 participants at risk Pembrolizumab 200 mg Q3W, IV on Day 1 of each 3-week cycle for up to 35 administrations (approximately 2 years).
Blood and lymphatic system disorders Autoimmune haemolytic anaemia	0.00% 0/53 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.	4.3% 1/23 • Number of events 1 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.
Blood and lymphatic system disorders Febrile neutropenia	1.9% 1/53 • Number of events 1 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.	13.0% 3/23 • Number of events 4 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.
Blood and lymphatic system disorders Neutropenia	0.00% 0/53 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.	4.3% 1/23 • Number of events 1 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/53 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.	4.3% 1/23 • Number of events 1 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.
Cardiac disorders Cardiac tamponade	1.9% 1/53 • Number of events 1 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.	0.00% 0/23 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.
Cardiac disorders Myocardial infarction	1.9% 1/53 • Number of events 1 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.	0.00% 0/23 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.
Cardiac disorders Pericardial effusion	1.9% 1/53 • Number of events 1 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.	0.00% 0/23 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.
Cardiac disorders Pericarditis	1.9% 1/53 • Number of events 1 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.	0.00% 0/23 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.
Cardiac disorders Supraventricular tachycardia	1.9% 1/53 • Number of events 2 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.	0.00% 0/23 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.
Cardiac disorders Tachycardia	1.9% 1/53 • Number of events 1 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.	0.00% 0/23 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.
Endocrine disorders Hypercalcaemia of malignancy	0.00% 0/53 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.	4.3% 1/23 • Number of events 1 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.
Endocrine disorders Hyperthyroidism	0.00% 0/53 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.	4.3% 1/23 • Number of events 1 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.
Gastrointestinal disorders Diarrhoea	1.9% 1/53 • Number of events 1 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.	0.00% 0/23 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.
Gastrointestinal disorders Gastric perforation	1.9% 1/53 • Number of events 1 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.	0.00% 0/23 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.
General disorders Death	0.00% 0/53 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.	4.3% 1/23 • Number of events 1 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.
General disorders General physical health deterioration	0.00% 0/53 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.	4.3% 1/23 • Number of events 1 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.
General disorders Pyrexia	1.9% 1/53 • Number of events 1 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.	0.00% 0/23 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.
Hepatobiliary disorders Cholecystitis	0.00% 0/53 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.	4.3% 1/23 • Number of events 1 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.
Infections and infestations Aspergillus infection	1.9% 1/53 • Number of events 1 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.	0.00% 0/23 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.
Infections and infestations Clostridium difficile infection	1.9% 1/53 • Number of events 1 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.	0.00% 0/23 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.
Infections and infestations Lower respiratory tract infection	0.00% 0/53 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.	4.3% 1/23 • Number of events 1 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.
Infections and infestations Pneumonia	1.9% 1/53 • Number of events 1 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.	0.00% 0/23 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.
Infections and infestations Sepsis	0.00% 0/53 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.	4.3% 1/23 • Number of events 1 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.
Infections and infestations Septic shock	0.00% 0/53 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.	4.3% 1/23 • Number of events 1 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.
Infections and infestations Staphylococcal infection	0.00% 0/53 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.	4.3% 1/23 • Number of events 1 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.
Infections and infestations Staphylococcal sepsis	0.00% 0/53 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.	4.3% 1/23 • Number of events 1 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.
Injury, poisoning and procedural complications Subdural haematoma	0.00% 0/53 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.	4.3% 1/23 • Number of events 1 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.
Investigations Aspartate aminotransferase increased	1.9% 1/53 • Number of events 1 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.	0.00% 0/23 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.
Investigations Hepatic enzyme increased	1.9% 1/53 • Number of events 1 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.	0.00% 0/23 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.
Metabolism and nutrition disorders Hypercalcaemia	0.00% 0/53 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.	8.7% 2/23 • Number of events 2 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.
Renal and urinary disorders Acute kidney injury	1.9% 1/53 • Number of events 1 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.	4.3% 1/23 • Number of events 1 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.
Renal and urinary disorders Urinary tract obstruction	0.00% 0/53 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.	4.3% 1/23 • Number of events 1 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.
Respiratory, thoracic and mediastinal disorders Dyspnoea	1.9% 1/53 • Number of events 1 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.	0.00% 0/23 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.
Respiratory, thoracic and mediastinal disorders Pleural effusion	1.9% 1/53 • Number of events 1 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.	4.3% 1/23 • Number of events 1 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	0.00% 0/53 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.	4.3% 1/23 • Number of events 1 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.
Respiratory, thoracic and mediastinal disorders Pneumonitis	1.9% 1/53 • Number of events 2 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.	4.3% 1/23 • Number of events 1 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.
Skin and subcutaneous tissue disorders Rash	0.00% 0/53 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.	4.3% 1/23 • Number of events 2 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.
Vascular disorders Hypotension	0.00% 0/53 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.	4.3% 1/23 • Number of events 1 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.
Vascular disorders Venous thrombosis	1.9% 1/53 • Number of events 1 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.	0.00% 0/23 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.

Other adverse events
Measure	Pembrolizumab: Relapsed or Refractory Primary Mediastinal Large B-cell Lymphoma (rrPMBCL) n=53 participants at risk Pembrolizumab 200 mg every 3 weeks (Q3W), intravenous infusion (IV) on Day 1 of each 3-week cycle for up to 35 administrations (approximately 2 years).	Pembrolizumab: Relapsed or Refractory Richter Syndrome (rrRS) n=23 participants at risk Pembrolizumab 200 mg Q3W, IV on Day 1 of each 3-week cycle for up to 35 administrations (approximately 2 years).
Investigations Aspartate aminotransferase increased	1.9% 1/53 • Number of events 2 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.	8.7% 2/23 • Number of events 2 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.
Blood and lymphatic system disorders Anaemia	11.3% 6/53 • Number of events 6 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.	30.4% 7/23 • Number of events 9 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.
Blood and lymphatic system disorders Leukopenia	7.5% 4/53 • Number of events 5 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.	8.7% 2/23 • Number of events 2 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.
Blood and lymphatic system disorders Lymph node pain	0.00% 0/53 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.	8.7% 2/23 • Number of events 2 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.
Blood and lymphatic system disorders Neutropenia	28.3% 15/53 • Number of events 29 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.	8.7% 2/23 • Number of events 2 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.
Blood and lymphatic system disorders Thrombocytopenia	3.8% 2/53 • Number of events 3 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.	13.0% 3/23 • Number of events 3 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.
Endocrine disorders Hypothyroidism	7.5% 4/53 • Number of events 4 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.	8.7% 2/23 • Number of events 2 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.
Gastrointestinal disorders Abdominal pain	9.4% 5/53 • Number of events 5 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.	13.0% 3/23 • Number of events 3 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.
Gastrointestinal disorders Constipation	7.5% 4/53 • Number of events 4 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.	13.0% 3/23 • Number of events 3 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.
Gastrointestinal disorders Diarrhoea	13.2% 7/53 • Number of events 9 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.	21.7% 5/23 • Number of events 5 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.
Gastrointestinal disorders Nausea	11.3% 6/53 • Number of events 8 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.	26.1% 6/23 • Number of events 7 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.
Gastrointestinal disorders Stomatitis	0.00% 0/53 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.	8.7% 2/23 • Number of events 2 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.
Gastrointestinal disorders Vomiting	9.4% 5/53 • Number of events 5 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.	8.7% 2/23 • Number of events 2 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.
General disorders Asthenia	13.2% 7/53 • Number of events 10 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.	8.7% 2/23 • Number of events 2 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.
General disorders Chest pain	7.5% 4/53 • Number of events 4 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.	0.00% 0/23 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.
General disorders Chills	0.00% 0/53 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.	13.0% 3/23 • Number of events 3 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.
General disorders Fatigue	11.3% 6/53 • Number of events 7 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.	34.8% 8/23 • Number of events 8 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.
General disorders Pyrexia	28.3% 15/53 • Number of events 25 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.	13.0% 3/23 • Number of events 4 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.
Infections and infestations Bronchitis	5.7% 3/53 • Number of events 3 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.	0.00% 0/23 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.
Infections and infestations Herpes zoster	5.7% 3/53 • Number of events 3 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.	4.3% 1/23 • Number of events 1 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.
Infections and infestations Nasopharyngitis	15.1% 8/53 • Number of events 10 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.	0.00% 0/23 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.
Infections and infestations Pharyngitis	5.7% 3/53 • Number of events 3 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.	0.00% 0/23 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.
Infections and infestations Rhinitis	9.4% 5/53 • Number of events 6 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.	0.00% 0/23 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.
Infections and infestations Upper respiratory tract infection	7.5% 4/53 • Number of events 5 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.	0.00% 0/23 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.
Infections and infestations Urinary tract infection	1.9% 1/53 • Number of events 1 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.	8.7% 2/23 • Number of events 2 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.
Infections and infestations Vulvovaginal mycotic infection	7.5% 4/53 • Number of events 5 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.	0.00% 0/23 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.
Investigations Blood alkaline phosphatase increased	1.9% 1/53 • Number of events 1 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.	8.7% 2/23 • Number of events 2 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.
Investigations Blood bilirubin increased	0.00% 0/53 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.	8.7% 2/23 • Number of events 2 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.
Investigations Blood creatinine increased	0.00% 0/53 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.	13.0% 3/23 • Number of events 3 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.
Metabolism and nutrition disorders Decreased appetite	3.8% 2/53 • Number of events 2 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.	13.0% 3/23 • Number of events 3 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.
Metabolism and nutrition disorders Hyperglycaemia	7.5% 4/53 • Number of events 5 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.	17.4% 4/23 • Number of events 4 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.
Metabolism and nutrition disorders Hyperkalaemia	0.00% 0/53 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.	13.0% 3/23 • Number of events 3 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.
Metabolism and nutrition disorders Hypokalaemia	3.8% 2/53 • Number of events 2 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.	8.7% 2/23 • Number of events 2 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.
Metabolism and nutrition disorders Hyponatraemia	3.8% 2/53 • Number of events 2 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.	8.7% 2/23 • Number of events 2 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.
Metabolism and nutrition disorders Hypophosphataemia	1.9% 1/53 • Number of events 1 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.	8.7% 2/23 • Number of events 2 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.
Musculoskeletal and connective tissue disorders Arthralgia	11.3% 6/53 • Number of events 7 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.	0.00% 0/23 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.
Musculoskeletal and connective tissue disorders Back pain	9.4% 5/53 • Number of events 5 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.	8.7% 2/23 • Number of events 2 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.
Musculoskeletal and connective tissue disorders Myalgia	5.7% 3/53 • Number of events 4 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.	0.00% 0/23 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.
Musculoskeletal and connective tissue disorders Pain in extremity	5.7% 3/53 • Number of events 3 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.	4.3% 1/23 • Number of events 1 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.
Nervous system disorders Dizziness	5.7% 3/53 • Number of events 3 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.	0.00% 0/23 • Serious adverse events (AEs), non-serious AEs and all-cause mortality was collected up to approximately 56 months through end of trial (EOT) data cut-off date 23 Oct 2020. All-cause mortality was reported on all allocated participants. Serious and non-serious AEs were reported among participants who received at least one dose of study treatment. Per protocol, disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to study drug were excluded.