Trial Outcomes & Findings for Safety and Efficacy of Pembrolizumab (MK-3475) in Combination With TS-1+Cisplatin or TS-1+Oxaliplatin as First Line Chemotherapy in Gastric Cancer (MK-3475-659/KEYNOTE-659) (NCT NCT03382600)

Last Updated: 2024-06-11

Results Overview

For the primary efficacy analysis, ORR was defined as the percentage of participants who have a best response of complete response (CR, disappearance of all target lesions) or partial response (PR, at least a 30% decrease in the sum of diameters \[SOD\] of target lesions, taking as reference the baseline SOD) per RECIST 1.1 as assessed by BICR.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

100 participants

Primary outcome timeframe

Up to ~36 months

Results posted on

2024-06-11

Participant Flow

Programmed cell death ligand 1 (PD-L1) positive, human epidermal growth factor receptor 2 (HER2)/neu negative participants 18 to 75 years of age with advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma were recruited at 25 study sites in Japan.

Participant milestones

Participant milestones
Measure	Pembrolizumab + Oxaliplatin +TS-1 (Cohort 1) Participants received pembrolizumab 200 mg every 3 weeks (Q3W) plus oxaliplatin 130 mg/m\^2 Q3W by intravenous (IV) infusion plus TS-1 twice daily (BID) by continuous oral administration for 14 days, followed by a recovery period of 7 days. Study treatment started on Day 1 of each 3-week course, and continued for up to \~3 years.	Pembrolizumab + Cisplatin +TS-1 (Cohort 2) Participants received pembrolizumab 200 mg Q3W plus cisplatin 60 mg/m\^2 Q3W by IV infusion plus TS-1 BID by continuous oral administration for 14 days, followed by a recovery period of 7 days. Study treatment started on Day 1 of each 3-week course, and continued for up to \~3 years.
Overall Study STARTED	54	46
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	54	46

Reasons for withdrawal

Reasons for withdrawal
Measure	Pembrolizumab + Oxaliplatin +TS-1 (Cohort 1) Participants received pembrolizumab 200 mg every 3 weeks (Q3W) plus oxaliplatin 130 mg/m\^2 Q3W by intravenous (IV) infusion plus TS-1 twice daily (BID) by continuous oral administration for 14 days, followed by a recovery period of 7 days. Study treatment started on Day 1 of each 3-week course, and continued for up to \~3 years.	Pembrolizumab + Cisplatin +TS-1 (Cohort 2) Participants received pembrolizumab 200 mg Q3W plus cisplatin 60 mg/m\^2 Q3W by IV infusion plus TS-1 BID by continuous oral administration for 14 days, followed by a recovery period of 7 days. Study treatment started on Day 1 of each 3-week course, and continued for up to \~3 years.
Overall Study Adverse Event	3	3
Overall Study Clinical Disease Progression	2	4
Overall Study Radiological Progression	40	31
Overall Study Withdrawal by Subject	0	1
Overall Study Other	9	7

Baseline Characteristics

Safety and Efficacy of Pembrolizumab (MK-3475) in Combination With TS-1+Cisplatin or TS-1+Oxaliplatin as First Line Chemotherapy in Gastric Cancer (MK-3475-659/KEYNOTE-659)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Pembrolizumab + Oxaliplatin +TS-1 (Cohort 1) n=54 Participants Participants received pembrolizumab 200 mg Q3W plus oxaliplatin 130 mg/m\^2 Q3W by IV infusion plus TS-1 BID by continuous oral administration for 14 days, followed by a recovery period of 7 days. Study treatment started on Day 1 of each 3-week course, and continued for up to \~3 years.	Pembrolizumab + Cisplatin +TS-1 (Cohort 2) n=46 Participants Participants received pembrolizumab 200 mg Q3W plus cisplatin 60 mg/m\^2 Q3W by IV infusion plus TS-1 BID by continuous oral administration for 14 days, followed by a recovery period of 7 days. Study treatment started on Day 1 of each 3-week course, and continued for up to \~3 years.	Total n=100 Participants Total of all reporting groups
Age, Continuous	61.5 years STANDARD_DEVIATION 11.6 • n=5 Participants	62.9 years STANDARD_DEVIATION 10.2 • n=7 Participants	62.1 years STANDARD_DEVIATION 10.9 • n=5 Participants
Sex: Female, Male Female	11 Participants n=5 Participants	18 Participants n=7 Participants	29 Participants n=5 Participants
Sex: Female, Male Male	43 Participants n=5 Participants	28 Participants n=7 Participants	71 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	54 Participants n=5 Participants	46 Participants n=7 Participants	100 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	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants	0 Participants n=7 Participants	0 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	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to ~36 months

Population: All participants who received ≥1 dose of study treatment are included.

Outcome measures

Outcome measures
Measure	Pembrolizumab + Oxaliplatin +TS-1 (Cohort 1) n=54 Participants Participants received pembrolizumab 200 mg Q3W plus oxaliplatin 130 mg/m\^2 Q3W by IV infusion plus TS-1 BID by continuous oral administration for 14 days, followed by a recovery period of 7 days. Study treatment started on Day 1 of each 3-week course, and continued for up to \~3 years.	Pembrolizumab + Cisplatin +TS-1 (Cohort 2) n=46 Participants Participants received pembrolizumab 200 mg Q3W plus cisplatin 60 mg/m\^2 Q3W by IV infusion plus TS-1 BID by continuous oral administration for 14 days, followed by a recovery period of 7 days. Study treatment started on Day 1 of each 3-week course, and continued for up to \~3 years.
Objective Response Rate (ORR) According to Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1) Assessed by Blinded Independent Central Review (BICR)	72.2 Percentage of participants Interval 58.4 to 83.5	80.4 Percentage of participants Interval 66.1 to 90.6

SECONDARY outcome

Timeframe: Up to ~36 months

Population: All participants who received ≥1 dose of study drug are included.

For the secondary efficacy analysis, ORR was defined as the percentage of participants whose best response based on imaging is CR (disappearance of all target lesions) or PR (≥30% decrease in the SOD of target lesions, taking as reference the baseline SOD) according to iRECIST as assessed by BICR. iRECIST is a modification to RECIST that takes into account unique patterns of atypical response in immunotherapy and enables treatment beyond initial radiographic progression.

Outcome measures

Outcome measures
Measure	Pembrolizumab + Oxaliplatin +TS-1 (Cohort 1) n=54 Participants Participants received pembrolizumab 200 mg Q3W plus oxaliplatin 130 mg/m\^2 Q3W by IV infusion plus TS-1 BID by continuous oral administration for 14 days, followed by a recovery period of 7 days. Study treatment started on Day 1 of each 3-week course, and continued for up to \~3 years.	Pembrolizumab + Cisplatin +TS-1 (Cohort 2) n=46 Participants Participants received pembrolizumab 200 mg Q3W plus cisplatin 60 mg/m\^2 Q3W by IV infusion plus TS-1 BID by continuous oral administration for 14 days, followed by a recovery period of 7 days. Study treatment started on Day 1 of each 3-week course, and continued for up to \~3 years.
ORR According to Immune-related Response Evaluation Criteria In Solid Tumors (iRECIST) Assessed by BICR	72.2 Percentage of participants Interval 58.4 to 83.5	80.4 Percentage of participants Interval 66.1 to 90.6

SECONDARY outcome

Timeframe: Up to ~36 months

Population: All participants who received ≥1 dose of study drug and had a confirmed response of CR or PR are included.

For participants who demonstrated complete response (CR, disappearance of all target lesions) or partial response (PR, ≥30% decrease in the SOD of target lesions) according to RECIST 1.1 as assessed by BICR, DOR was defined as the time from the earliest date of qualifying response (CR or PR) until earliest date of progressive disease (PD, ≥20% increase in the SOD of target lesions) or death from any cause, whichever came first. DOR was censored at the last tumor assessment date if a responder did not have PD or death.

Outcome measures

Outcome measures
Measure	Pembrolizumab + Oxaliplatin +TS-1 (Cohort 1) n=39 Participants Participants received pembrolizumab 200 mg Q3W plus oxaliplatin 130 mg/m\^2 Q3W by IV infusion plus TS-1 BID by continuous oral administration for 14 days, followed by a recovery period of 7 days. Study treatment started on Day 1 of each 3-week course, and continued for up to \~3 years.	Pembrolizumab + Cisplatin +TS-1 (Cohort 2) n=37 Participants Participants received pembrolizumab 200 mg Q3W plus cisplatin 60 mg/m\^2 Q3W by IV infusion plus TS-1 BID by continuous oral administration for 14 days, followed by a recovery period of 7 days. Study treatment started on Day 1 of each 3-week course, and continued for up to \~3 years.
Duration of Response (DOR) According to RECIST 1.1 Assessed by BICR	10.6 months Interval 5.6 to Insufficient events to calculate the upper bound of the confidence interval.	9.5 months Interval 4.7 to 15.3

SECONDARY outcome

Timeframe: Up to ~36 months

Population: All participants who received ≥1 dose of study drug and had a confirmed response of CR or PR are included.

For participants who demonstrated complete response (CR, disappearance of all target lesions) or partial response (PR, ≥30% decrease in the SOD of target lesions) according to iRECIST as assessed by BICR, DOR was defined as the time from the earliest date of qualifying response (CR or PR) until earliest date of progressive disease (PD, ≥20% increase in the SOD of target lesions) or death from any cause, whichever came first. DOR was censored at the last tumor assessment date if a responder did not have PD or death. iRECIST is a modification to RECIST that takes into account unique patterns of atypical response in immunotherapy and enables treatment beyond initial radiographic progression.

Outcome measures

Outcome measures
Measure	Pembrolizumab + Oxaliplatin +TS-1 (Cohort 1) n=39 Participants Participants received pembrolizumab 200 mg Q3W plus oxaliplatin 130 mg/m\^2 Q3W by IV infusion plus TS-1 BID by continuous oral administration for 14 days, followed by a recovery period of 7 days. Study treatment started on Day 1 of each 3-week course, and continued for up to \~3 years.	Pembrolizumab + Cisplatin +TS-1 (Cohort 2) n=37 Participants Participants received pembrolizumab 200 mg Q3W plus cisplatin 60 mg/m\^2 Q3W by IV infusion plus TS-1 BID by continuous oral administration for 14 days, followed by a recovery period of 7 days. Study treatment started on Day 1 of each 3-week course, and continued for up to \~3 years.
DOR According to iRECIST Assessed by BICR	10.6 months Interval 5.6 to Insufficient events to calculate the upper bound of the confidence interval.	9.5 months Interval 4.7 to Insufficient events to calculate the upper bound of the confidence interval.

SECONDARY outcome

Timeframe: Up to ~36 months

Population: All participants who received ≥1 dose of study drug are included.

DCR was defined as the percentage of participants in the analysis population who have complete response (CR, disappearance of all target lesions), partial response (PR (≥30% decrease in the SOD of target lesions, taking as reference the baseline SOD), or stable disease (SD, neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD, ≥20% increase in the SOD of target lesions\]). Responses are according to RECIST 1.1 as assessed by BICR.

Outcome measures

Outcome measures
Measure	Pembrolizumab + Oxaliplatin +TS-1 (Cohort 1) n=54 Participants Participants received pembrolizumab 200 mg Q3W plus oxaliplatin 130 mg/m\^2 Q3W by IV infusion plus TS-1 BID by continuous oral administration for 14 days, followed by a recovery period of 7 days. Study treatment started on Day 1 of each 3-week course, and continued for up to \~3 years.	Pembrolizumab + Cisplatin +TS-1 (Cohort 2) n=46 Participants Participants received pembrolizumab 200 mg Q3W plus cisplatin 60 mg/m\^2 Q3W by IV infusion plus TS-1 BID by continuous oral administration for 14 days, followed by a recovery period of 7 days. Study treatment started on Day 1 of each 3-week course, and continued for up to \~3 years.
Disease Control Rate (DCR) According to RECIST 1.1 Assessed by BICR	96.3 Percentage of participants Interval 87.3 to 99.5	97.8 Percentage of participants Interval 88.5 to 99.9

SECONDARY outcome

Timeframe: Up to ~36 months

Population: All participants who received ≥1 dose of study drug are included.

DCR was defined as the percentage of participants in the analysis population who have CR (disappearance of all target lesions), PR (≥30% decrease in the SOD of target lesions, taking as reference the baseline SOD), or stable disease (SD, neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD \[≥20% increase in the SOD of target lesions\]). Responses are according to iRECIST 1.1 as assessed by BICR. iRECIST is a modification to RECIST that takes into account unique patterns of atypical response in immunotherapy and enables treatment beyond initial radiographic progression.

Outcome measures

Outcome measures
Measure	Pembrolizumab + Oxaliplatin +TS-1 (Cohort 1) n=54 Participants Participants received pembrolizumab 200 mg Q3W plus oxaliplatin 130 mg/m\^2 Q3W by IV infusion plus TS-1 BID by continuous oral administration for 14 days, followed by a recovery period of 7 days. Study treatment started on Day 1 of each 3-week course, and continued for up to \~3 years.	Pembrolizumab + Cisplatin +TS-1 (Cohort 2) n=46 Participants Participants received pembrolizumab 200 mg Q3W plus cisplatin 60 mg/m\^2 Q3W by IV infusion plus TS-1 BID by continuous oral administration for 14 days, followed by a recovery period of 7 days. Study treatment started on Day 1 of each 3-week course, and continued for up to \~3 years.
DCR According to iRECIST 1.1 Assessed by BICR	96.3 Percentage of participants Interval 87.3 to 99.5	97.8 Percentage of participants Interval 88.5 to 99.9

SECONDARY outcome

Timeframe: Up to ~36 months

Population: All participants who received ≥1 dose of study drug are included.

Outcome measures

Outcome measures
Measure	Pembrolizumab + Oxaliplatin +TS-1 (Cohort 1) n=54 Participants Participants received pembrolizumab 200 mg Q3W plus oxaliplatin 130 mg/m\^2 Q3W by IV infusion plus TS-1 BID by continuous oral administration for 14 days, followed by a recovery period of 7 days. Study treatment started on Day 1 of each 3-week course, and continued for up to \~3 years.	Pembrolizumab + Cisplatin +TS-1 (Cohort 2) n=46 Participants Participants received pembrolizumab 200 mg Q3W plus cisplatin 60 mg/m\^2 Q3W by IV infusion plus TS-1 BID by continuous oral administration for 14 days, followed by a recovery period of 7 days. Study treatment started on Day 1 of each 3-week course, and continued for up to \~3 years.
Time to Response (TTR) According to RECIST 1.1 Assessed by BICR	1.5 months Interval 1.3 to 5.5	1.5 months Interval 1.2 to 2.9

SECONDARY outcome

Timeframe: Up to ~36 months

Population: All participants who received ≥1 dose of study drug are included.

TTR was defined as the time from the date of enrollment day to the first date of confirmed CR (disappearance of all target lesions) or PR (≥30% decrease in the SOD of target lesions, taking as reference the baseline SOD). Responses are according to iRECIST 1.1 as assessed by BICR. iRECIST is a modification to RECIST that takes into account unique patterns of atypical response in immunotherapy and enables treatment beyond initial radiographic progression.

Outcome measures

Outcome measures
Measure	Pembrolizumab + Oxaliplatin +TS-1 (Cohort 1) n=54 Participants Participants received pembrolizumab 200 mg Q3W plus oxaliplatin 130 mg/m\^2 Q3W by IV infusion plus TS-1 BID by continuous oral administration for 14 days, followed by a recovery period of 7 days. Study treatment started on Day 1 of each 3-week course, and continued for up to \~3 years.	Pembrolizumab + Cisplatin +TS-1 (Cohort 2) n=46 Participants Participants received pembrolizumab 200 mg Q3W plus cisplatin 60 mg/m\^2 Q3W by IV infusion plus TS-1 BID by continuous oral administration for 14 days, followed by a recovery period of 7 days. Study treatment started on Day 1 of each 3-week course, and continued for up to \~3 years.
TTR According to iRECIST 1.1 Assessed by BICR	1.5 months Interval 1.3 to 5.5	1.5 months Interval 1.2 to 2.9

SECONDARY outcome

Timeframe: Up to ~36 months

Population: All participants who received ≥1 dose of study drug are included.

Outcome measures

Outcome measures
Measure	Pembrolizumab + Oxaliplatin +TS-1 (Cohort 1) n=54 Participants Participants received pembrolizumab 200 mg Q3W plus oxaliplatin 130 mg/m\^2 Q3W by IV infusion plus TS-1 BID by continuous oral administration for 14 days, followed by a recovery period of 7 days. Study treatment started on Day 1 of each 3-week course, and continued for up to \~3 years.	Pembrolizumab + Cisplatin +TS-1 (Cohort 2) n=46 Participants Participants received pembrolizumab 200 mg Q3W plus cisplatin 60 mg/m\^2 Q3W by IV infusion plus TS-1 BID by continuous oral administration for 14 days, followed by a recovery period of 7 days. Study treatment started on Day 1 of each 3-week course, and continued for up to \~3 years.
Progression-free Survival (PFS) According to RECIST 1.1 Assessed by BICR	9.4 months Interval 6.6 to 12.6	8.3 months Interval 5.8 to 15.3

SECONDARY outcome

Timeframe: Up to ~36 months

Population: All participants who received ≥1 dose of study drug are included.

PFS was defined as the time from the date of enrollment day to the first documented PD (defined as ≥20% increase in the SOD of target lesions) or death due to any cause, whichever occurred first. Responses are according to iRECIST 1.1 as assessed by BICR. iRECIST is a modification to RECIST that takes into account unique patterns of atypical response in immunotherapy and enables treatment beyond initial radiographic progression.

Outcome measures

Outcome measures
Measure	Pembrolizumab + Oxaliplatin +TS-1 (Cohort 1) n=54 Participants Participants received pembrolizumab 200 mg Q3W plus oxaliplatin 130 mg/m\^2 Q3W by IV infusion plus TS-1 BID by continuous oral administration for 14 days, followed by a recovery period of 7 days. Study treatment started on Day 1 of each 3-week course, and continued for up to \~3 years.	Pembrolizumab + Cisplatin +TS-1 (Cohort 2) n=46 Participants Participants received pembrolizumab 200 mg Q3W plus cisplatin 60 mg/m\^2 Q3W by IV infusion plus TS-1 BID by continuous oral administration for 14 days, followed by a recovery period of 7 days. Study treatment started on Day 1 of each 3-week course, and continued for up to \~3 years.
PFS According to iRECIST 1.1 Assessed by BICR	9.4 months Interval 6.6 to 12.6	10.9 months Interval 6.7 to Insufficient events to calculate the upper bound of the confidence interval.

SECONDARY outcome

Timeframe: Up to ~36 months

Population: All participants who received ≥1 dose of study drug are included.

OS was defined as the time from the date of enrollment day to death due to any cause. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up. For these participants, date of last follow up was last visit date instead of death date.

Outcome measures

Outcome measures
Measure	Pembrolizumab + Oxaliplatin +TS-1 (Cohort 1) n=54 Participants Participants received pembrolizumab 200 mg Q3W plus oxaliplatin 130 mg/m\^2 Q3W by IV infusion plus TS-1 BID by continuous oral administration for 14 days, followed by a recovery period of 7 days. Study treatment started on Day 1 of each 3-week course, and continued for up to \~3 years.	Pembrolizumab + Cisplatin +TS-1 (Cohort 2) n=46 Participants Participants received pembrolizumab 200 mg Q3W plus cisplatin 60 mg/m\^2 Q3W by IV infusion plus TS-1 BID by continuous oral administration for 14 days, followed by a recovery period of 7 days. Study treatment started on Day 1 of each 3-week course, and continued for up to \~3 years.
Overall Survival (OS)	16.9 months Interval 13.4 to 20.0	17.1 months Interval 12.6 to 23.1

SECONDARY outcome

Timeframe: Up to ~36 months

Population: All participants who received ≥1 dose of study drug are included.

An AE is any untoward medical occurrence in a participant that is temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study treatment

Outcome measures

Outcome measures
Measure	Pembrolizumab + Oxaliplatin +TS-1 (Cohort 1) n=54 Participants Participants received pembrolizumab 200 mg Q3W plus oxaliplatin 130 mg/m\^2 Q3W by IV infusion plus TS-1 BID by continuous oral administration for 14 days, followed by a recovery period of 7 days. Study treatment started on Day 1 of each 3-week course, and continued for up to \~3 years.	Pembrolizumab + Cisplatin +TS-1 (Cohort 2) n=46 Participants Participants received pembrolizumab 200 mg Q3W plus cisplatin 60 mg/m\^2 Q3W by IV infusion plus TS-1 BID by continuous oral administration for 14 days, followed by a recovery period of 7 days. Study treatment started on Day 1 of each 3-week course, and continued for up to \~3 years.
Number of Participants With ≥1 Adverse Event (AE)	54 Participants	46 Participants

SECONDARY outcome

Timeframe: Up to ~36 months

Population: All participants who received ≥1 dose of study drug are included.

Outcome measures

Outcome measures
Measure	Pembrolizumab + Oxaliplatin +TS-1 (Cohort 1) n=54 Participants Participants received pembrolizumab 200 mg Q3W plus oxaliplatin 130 mg/m\^2 Q3W by IV infusion plus TS-1 BID by continuous oral administration for 14 days, followed by a recovery period of 7 days. Study treatment started on Day 1 of each 3-week course, and continued for up to \~3 years.	Pembrolizumab + Cisplatin +TS-1 (Cohort 2) n=46 Participants Participants received pembrolizumab 200 mg Q3W plus cisplatin 60 mg/m\^2 Q3W by IV infusion plus TS-1 BID by continuous oral administration for 14 days, followed by a recovery period of 7 days. Study treatment started on Day 1 of each 3-week course, and continued for up to \~3 years.
Number of Participants Discontinuing From Study Treatment Due to AE(s)	3 Participants	3 Participants

Adverse Events

Pembrolizumab + Oxaliplatin +TS-1 (Cohort 1)

Serious events: 27 serious events

Other events: 54 other events

Deaths: 3 deaths

Pembrolizumab + Cisplatin +TS-1 (Cohort 2)

Serious events: 22 serious events

Other events: 46 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme LLC

Phone: 1-800-672-6372

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee If publication activity is not directed by the sponsor, the investigator agrees to submit all manuscripts or abstracts to the sponsor before submission.
Publication restrictions are in place

Restriction type: OTHER

Serious adverse events
Measure	Pembrolizumab + Oxaliplatin +TS-1 (Cohort 1) n=54 participants at risk Participants received pembrolizumab 200 mg Q3W plus oxaliplatin 130 mg/m\^2 Q3W by IV infusion plus TS-1 BID by continuous oral administration for 14 days, followed by a recovery period of 7 days. Study treatment started on Day 1 of each 3-week course, and continued for up to \~3 years.	Pembrolizumab + Cisplatin +TS-1 (Cohort 2) n=46 participants at risk Participants received pembrolizumab 200 mg Q3W plus cisplatin 60 mg/m\^2 Q3W by IV infusion plus TS-1 BID by continuous oral administration for 14 days, followed by a recovery period of 7 days. Study treatment started on Day 1 of each 3-week course, and continued for up to \~3 years.
Blood and lymphatic system disorders Disseminated intravascular coagulation	1.9% 1/54 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.	0.00% 0/46 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.
Blood and lymphatic system disorders Febrile neutropenia	3.7% 2/54 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.	0.00% 0/46 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.
Cardiac disorders Cardiac arrest	1.9% 1/54 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.	0.00% 0/46 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.
Cardiac disorders Cardiac ventricular thrombosis	1.9% 1/54 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.	0.00% 0/46 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.
Endocrine disorders Adrenal insufficiency	5.6% 3/54 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.	6.5% 3/46 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.
Endocrine disorders Hyperthyroidism	0.00% 0/54 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.	2.2% 1/46 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.
Endocrine disorders Hypopituitarism	0.00% 0/54 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.	2.2% 1/46 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.
Eye disorders Cataract	0.00% 0/54 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.	2.2% 1/46 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.
Eye disorders Glaucoma	0.00% 0/54 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.	2.2% 1/46 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.
Gastrointestinal disorders Abdominal pain	0.00% 0/54 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.	4.3% 2/46 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.
Gastrointestinal disorders Autoimmune colitis	0.00% 0/54 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.	2.2% 1/46 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.
Gastrointestinal disorders Colitis	3.7% 2/54 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.	0.00% 0/46 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.
Gastrointestinal disorders Constipation	0.00% 0/54 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.	2.2% 1/46 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.
Gastrointestinal disorders Diarrhoea	0.00% 0/54 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.	2.2% 1/46 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.
Gastrointestinal disorders Enteritis	1.9% 1/54 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.	0.00% 0/46 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.
Gastrointestinal disorders Enterocolitis	3.7% 2/54 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.	0.00% 0/46 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.
Gastrointestinal disorders Gastric perforation	1.9% 1/54 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.	0.00% 0/46 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.
Gastrointestinal disorders Nausea	1.9% 1/54 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.	2.2% 1/46 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.
Gastrointestinal disorders Oesophageal stenosis	1.9% 1/54 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.	0.00% 0/46 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.
Gastrointestinal disorders Pancreatic pseudocyst	1.9% 1/54 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.	0.00% 0/46 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.
Gastrointestinal disorders Pancreatitis	1.9% 1/54 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.	0.00% 0/46 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.
Gastrointestinal disorders Small intestinal perforation	0.00% 0/54 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.	2.2% 1/46 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.
Gastrointestinal disorders Vomiting	3.7% 2/54 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.	0.00% 0/46 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.
General disorders Malaise	0.00% 0/54 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.	2.2% 1/46 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.
General disorders Pyrexia	1.9% 1/54 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.	0.00% 0/46 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.
Hepatobiliary disorders Bile duct stone	0.00% 0/54 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.	2.2% 1/46 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.
Hepatobiliary disorders Cholecystitis	1.9% 1/54 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.	0.00% 0/46 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.
Hepatobiliary disorders Cholecystitis acute	0.00% 0/54 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.	2.2% 1/46 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.
Hepatobiliary disorders Hepatic function abnormal	0.00% 0/54 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.	2.2% 1/46 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.
Hepatobiliary disorders Hepatitis	0.00% 0/54 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.	2.2% 1/46 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.
Hepatobiliary disorders Hepatobiliary disease	0.00% 0/54 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.	2.2% 1/46 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.
Infections and infestations Appendicitis	1.9% 1/54 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.	0.00% 0/46 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.
Infections and infestations Cytomegalovirus enterocolitis	1.9% 1/54 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.	0.00% 0/46 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.
Infections and infestations Enteritis infectious	1.9% 1/54 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.	0.00% 0/46 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.
Infections and infestations Gastroenteritis	0.00% 0/54 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.	2.2% 1/46 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.
Infections and infestations Herpes zoster	0.00% 0/54 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.	2.2% 1/46 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.
Infections and infestations Pneumonia	0.00% 0/54 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.	6.5% 3/46 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.
Injury, poisoning and procedural complications Anastomotic stenosis	0.00% 0/54 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.	2.2% 1/46 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.
Injury, poisoning and procedural complications Fall	0.00% 0/54 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.	2.2% 1/46 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.
Injury, poisoning and procedural complications Lumbar vertebral fracture	0.00% 0/54 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.	2.2% 1/46 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.

Other adverse events
Measure	Pembrolizumab + Oxaliplatin +TS-1 (Cohort 1) n=54 participants at risk Participants received pembrolizumab 200 mg Q3W plus oxaliplatin 130 mg/m\^2 Q3W by IV infusion plus TS-1 BID by continuous oral administration for 14 days, followed by a recovery period of 7 days. Study treatment started on Day 1 of each 3-week course, and continued for up to \~3 years.	Pembrolizumab + Cisplatin +TS-1 (Cohort 2) n=46 participants at risk Participants received pembrolizumab 200 mg Q3W plus cisplatin 60 mg/m\^2 Q3W by IV infusion plus TS-1 BID by continuous oral administration for 14 days, followed by a recovery period of 7 days. Study treatment started on Day 1 of each 3-week course, and continued for up to \~3 years.
Infections and infestations Bronchitis	5.6% 3/54 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.	0.00% 0/46 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.
Blood and lymphatic system disorders Anaemia	24.1% 13/54 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.	39.1% 18/46 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.
Blood and lymphatic system disorders Febrile neutropenia	7.4% 4/54 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.	2.2% 1/46 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.
Blood and lymphatic system disorders Neutropenia	5.6% 3/54 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.	13.0% 6/46 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.
Ear and labyrinth disorders Vertigo	5.6% 3/54 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.	0.00% 0/46 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.
Endocrine disorders Adrenal insufficiency	5.6% 3/54 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.	6.5% 3/46 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.
Endocrine disorders Hypothyroidism	9.3% 5/54 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.	6.5% 3/46 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.
Eye disorders Cataract	0.00% 0/54 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.	6.5% 3/46 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.
Eye disorders Lacrimation increased	9.3% 5/54 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.	4.3% 2/46 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.
Gastrointestinal disorders Abdominal pain	5.6% 3/54 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.	6.5% 3/46 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.
Gastrointestinal disorders Cheilitis	0.00% 0/54 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.	8.7% 4/46 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.
Gastrointestinal disorders Colitis	7.4% 4/54 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.	0.00% 0/46 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.
Gastrointestinal disorders Constipation	44.4% 24/54 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.	65.2% 30/46 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.
Gastrointestinal disorders Diarrhoea	44.4% 24/54 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.	47.8% 22/46 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.
Gastrointestinal disorders Nausea	63.0% 34/54 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.	60.9% 28/46 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.
Gastrointestinal disorders Stomatitis	29.6% 16/54 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.	37.0% 17/46 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.
Gastrointestinal disorders Vomiting	24.1% 13/54 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.	23.9% 11/46 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.
General disorders Fatigue	22.2% 12/54 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.	32.6% 15/46 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.
General disorders Malaise	40.7% 22/54 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.	32.6% 15/46 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.
General disorders Oedema	9.3% 5/54 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.	8.7% 4/46 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.
General disorders Oedema peripheral	14.8% 8/54 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.	15.2% 7/46 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.
General disorders Pyrexia	24.1% 13/54 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.	21.7% 10/46 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.
General disorders Infusion site extravasation	0.00% 0/54 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.	6.5% 3/46 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.
Immune system disorders Hypersensitivity	5.6% 3/54 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.	0.00% 0/46 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.
Infections and infestations Nasopharyngitis	5.6% 3/54 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.	17.4% 8/46 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.
Infections and infestations Pneumonia	3.7% 2/54 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.	6.5% 3/46 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.
Infections and infestations Upper respiratory tract infection	5.6% 3/54 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.	0.00% 0/46 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.
Injury, poisoning and procedural complications Infusion related reaction	5.6% 3/54 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.	0.00% 0/46 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.
Investigations Alanine aminotransferase increased	16.7% 9/54 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.	13.0% 6/46 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.
Investigations Aspartate aminotransferase increased	22.2% 12/54 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.	19.6% 9/46 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.
Investigations Blood bilirubin increased	7.4% 4/54 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.	4.3% 2/46 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.
Investigations Blood creatinine increased	1.9% 1/54 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.	13.0% 6/46 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.
Investigations Gamma-glutamyltransferase increased	3.7% 2/54 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.	6.5% 3/46 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.
Investigations Neutrophil count decreased	44.4% 24/54 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.	69.6% 32/46 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.
Investigations Platelet count decreased	53.7% 29/54 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.	23.9% 11/46 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.
Investigations Weight decreased	13.0% 7/54 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.	10.9% 5/46 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.
Investigations Weight increased	0.00% 0/54 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.	6.5% 3/46 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.
Investigations White blood cell count decreased	14.8% 8/54 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.	21.7% 10/46 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.
Investigations Blood alkaline phosphatase increased	5.6% 3/54 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.	6.5% 3/46 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.
Metabolism and nutrition disorders Hyperglycaemia	0.00% 0/54 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.	6.5% 3/46 • Up to ~36 months All participants who received ≥1 dose of study drug are included. 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", "Disease progression" unrelated to study drug are excluded as AEs.