Efficacy Study of Nivolumab Plus Ipilimumab or Nivolumab Plus Chemotherapy Against Chemotherapy in Stomach Cancer or Stomach/Esophagus Junction Cancer (CheckMate649)

• ClinicalTrials.gov Identifier: NCT02872116
• Recruitment Status: Active, not recruiting
• First Posted: August 19, 2016
• Results First Posted: June 28, 2022
• Last Update Posted: December 4, 2023
• Sponsor: Bristol-Myers Squibb
• Collaborator: Ono Pharmaceutical Co. Ltd
• Information provided by (Responsible Party): Bristol-Myers Squibb

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Conditions: Gastric Cancer; Gastroesophageal Junction Cancer; Esophageal Adenocarcinoma
• Interventions: Drug: Nivolumab; Drug: Ipilimumab; Drug: Oxaliplatin; Drug: Capecitabine; Drug: Leucovorin; Drug: Fluorouracil
• Enrollment: 2031

Participant Flow

Recruitment Details
Pre-assignment Details	2031 Participants Randomized and 1991 Treated

Arm/Group Title	Arm 1: Nivolumab + Chemotherapy (XELOX or FOLFOX)	Arm 2: Chemotherapy (XELOX or FOLFOX)	Arm 3: Nivolumab + Ipilimumab
Arm/Group Description	Nivolumab + Xelox: Nivolumab 360 mg IV over 30 minutes on Day 1 of each treatment cycle, every 3 weeks + Oxaliplatin 130 mg/m2 IV on Day 1 of each treatment cycle + capecitabine 1000 mg/m2 orally twice daily (ie, 1000 mg/m2 in the morning and 1000 mg/m2 in the evening) on Days 1 to 14 of each treatment cycle, every 3 weeks Nivolumab + Folfox: Nivolumab 240 mg IV over 30 minutes on Day 1 of each treatment cycle, every 2 weeks + Oxaliplatin 85 mg/m2 + leucovorin 400 mg/m2 + fluorouracil 400 mg/m2 IV on Day 1 of each treatment cycle, and fluorouracil 1200 mg/m2 IV continuous infusion over 24 hours (or per local standard) daily on Days 1 and 2 of each treatment cycle, every 2 weeks	Chemotherapy (XELOX or FOLFOX): Xelox: Oxaliplatin 130 mg/m2 IV on Day 1 of each treatment cycle + capecitabine 1000 mg/m2 orally twice daily (ie, 1000 mg/m2 in the morning and 1000 mg/m2 in the evening) on Days 1 to 14 of each treatment cycle, every 3 weeks. Folfox: Oxaliplatin 85 mg/m2 + leucovorin 400 mg/m2 + fluorouracil 400 mg/m2 IV on Day 1 of each treatment cycle, and fluorouracil 1200 mg/m2 IV continuous infusion over 24 hours (or per local standard) daily on Days 1 and 2 of each treatment cycle, every 2 weeks. This chemotherapy group consists of the two comparison chemotherapy sub-groups. Arm 2a (792 participants) is the comparison group to Arm 1 and Arm 2b (404 participants) is the comparison group to Arm 3. Some participants were counted in both Arm 2a and Arm 2b.	1 mg/kg nivolumab administered IV over 30 minutes followed by ipilimumab 3 mg/kg administered IV over 30 minutes on Day 1 of each treatment cycle every 3 weeks for 4 doses (Cycles 1 to 4), followed by nivolumab 240 mg administered IV over 30 minutes on Day 1 of each treatment cycle every 2 weeks (Cycle 5 and beyond). Arm is closed to enrollment as of 05-June-2018.
Period Title: Pre-Treatment
Started [1]	789	833	409
Completed [2]	782	806	403
Not Completed	7	27	6
Reason Not Completed
Disease Progression	0	1	0
Adverse event unrelated to study drug	0	2	1
Participants request to discontinue study treatment	0	2	0
Participant withdrew consent	2	20	3
Participant no longer meets study criteria	4	0	0
Other reasons	1	2	2
[1] = Randomized; [2] = Moving to treatment period
Period Title: Treatment
Started [1]	782	806	403
Completed [2]	623	653	319
Not Completed	159	153	84
Reason Not Completed
Death	122	94	68
Lost to Follow-up	5	7	3
Participant withdrew consent	20	40	8
Other reasons	12	12	5
[1] Treated; [2] Continuing in the study

Baseline Characteristics

Arm/Group Title		Arm 1: Nivolumab + Chemotherapy (XELOX or FOLFOX)	Arm 2: Chemotherapy (XELOX or FOLFOX)	Arm 3: Nivolumab + Ipilimumab	Total
Arm/Group Description		Nivolumab + Xelox: Nivolumab 360 mg IV over 30 minutes on Day 1 of each treatment cycle, every 3 weeks + Oxaliplatin 130 mg/m2 IV on Day 1 of each treatment cycle + capecitabine 1000 mg/m2 orally twice daily (ie, 1000 mg/m2 in the morning and 1000 mg/m2 in the evening) on Days 1 to 14 of each treatment cycle, every 3 weeks Nivolumab + Folfox: Nivolumab 240 mg IV over 30 minutes on Day 1 of each treatment cycle, every 2 weeks + Oxaliplatin 85 mg/m2 + leucovorin 400 mg/m2 + fluorouracil 400 mg/m2 IV on Day 1 of each treatment cycle, and fluorouracil 1200 mg/m2 IV continuous infusion over 24 hours (or per local standard) daily on Days 1 and 2 of each treatment cycle, every 2 weeks	Chemotherapy (XELOX or FOLFOX): Xelox: Oxaliplatin 130 mg/m2 IV on Day 1 of each treatment cycle + capecitabine 1000 mg/m2 orally twice daily (ie, 1000 mg/m2 in the morning and 1000 mg/m2 in the evening) on Days 1 to 14 of each treatment cycle, every 3 weeks. Folfox: Oxaliplatin 85 mg/m2 + leucovorin 400 mg/m2 + fluorouracil 400 mg/m2 IV on Day 1 of each treatment cycle, and fluorouracil 1200 mg/m2 IV continuous infusion over 24 hours (or per local standard) daily on Days 1 and 2 of each treatment cycle, every 2 weeks. This chemotherapy group consists of the two comparison chemotherapy sub-groups. Arm 2a (792 participants) is the comparison group to Arm 1 and Arm 2b (404 participants) is the comparison group to Arm 3. Some participants were counted in both Arm 2a and Arm 2b.	1 mg/kg nivolumab administered IV over 30 minutes followed by ipilimumab 3 mg/kg administered IV over 30 minutes on Day 1 of each treatment cycle every 3 weeks for 4 doses (Cycles 1 to 4), followed by nivolumab 240 mg administered IV over 30 minutes on Day 1 of each treatment cycle every 2 weeks (Cycle 5 and beyond). Arm is closed to enrollment as of 05-June-2018.	Total of all reporting groups
Overall Number of Baseline Participants		789	833	409	2031
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	789 participants	833 participants	409 participants	2031 participants
		60.3 (11.9)	59.8 (12.1)	59.4 (11.7)	59.9 (12.0)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	789 participants	833 participants	409 participants	2031 participants
	Female	249 31.6%	246 29.5%	131 32.0%	626 30.8%
	Male	540 68.4%	587 70.5%	278 68.0%	1405 69.2%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	789 participants	833 participants	409 participants	2031 participants
	American Indian or Alaska Native	12 1.5%	13 1.6%	1 0.2%	26 1.3%
	Asian	186 23.6%	200 24.0%	124 30.3%	510 25.1%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Black or African American	7 0.9%	11 1.3%	6 1.5%	24 1.2%
	White	556 70.5%	570 68.4%	264 64.5%	1390 68.4%
	More than one race	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported	28 3.5%	39 4.7%	14 3.4%	81 4.0%

Outcome Measures

1. Primary Outcome

Title	Overall Survival (OS) in Participants Treated With Nivolumab Plus Chemotherapy vs Chemotherapy With PD-L1 CPS ≥ 5
Description	Overall survival (OS), defined as the time from randomization to the time of death, in participants treated with Nivolumab plus Chemotherapy vs Chemotherapy with PD-L1 CPS (combined positive score) ≥ 5. CPS is defined as the number of PD-L1 staining cells (tumor cells, lymphocytes, macrophages) divided by the total number of viable tumor cells, multiplied by 100.
Time Frame	From the date of randomization up to the date of death, up to approximately 17 months

Outcome Measure Data

Analysis Population Description

All randomized participants with PD-L1 CPS ≥ 5

Arm/Group Title	Arm 1: Nivolumab + Chemotherapy (XELOX or FOLFOX)	Arm 2a: Chemotherapy (XELOX or FOLFOX)
Arm/Group Description:	Nivolumab + Xelox: Nivolumab 360 mg IV over 30 minutes on Day 1 of each treatment cycle, every 3 weeks + Oxaliplatin 130 mg/m2 IV on Day 1 of each treatment cycle + capecitabine 1000 mg/m2 orally twice daily (ie, 1000 mg/m2 in the morning and 1000 mg/m2 in the evening) on Days 1 to 14 of each treatment cycle, every 3 weeks Nivolumab + Folfox: Nivolumab 240 mg IV over 30 minutes on Day 1 of each treatment cycle, every 2 weeks + Oxaliplatin 85 mg/m2 + leucovorin 400 mg/m2 + fluorouracil 400 mg/m2 IV on Day 1 of each treatment cycle, and fluorouracil 1200 mg/m2 IV continuous infusion over 24 hours (or per local standard) daily on Days 1 and 2 of each treatment cycle, every 2 weeks	Chemotherapy (XELOX or FOLFOX): Xelox: Oxaliplatin 130 mg/m2 IV on Day 1 of each treatment cycle + capecitabine 1000 mg/m2 orally twice daily (ie, 1000 mg/m2 in the morning and 1000 mg/m2 in the evening) on Days 1 to 14 of each treatment cycle, every 3 weeks. Folfox: Oxaliplatin 85 mg/m2 + leucovorin 400 mg/m2 + fluorouracil 400 mg/m2 IV on Day 1 of each treatment cycle, and fluorouracil 1200 mg/m2 IV continuous infusion over 24 hours (or per local standard) daily on Days 1 and 2 of each treatment cycle, every 2 weeks. Comparison group to Arm 1.
Overall Number of Participants Analyzed	473	482
Median (95% Confidence Interval); Unit of Measure: Months
	14.39; (13.11 to 16.23)	11.10; (10.02 to 12.09)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm 1: Nivolumab + Chemotherapy (XELOX or FOLFOX), Arm 2a: Chemotherapy (XELOX or FOLFOX)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.71
	Confidence Interval	(2-Sided) 98.4%; 0.59 to 0.86
	Estimation Comments	[Not Specified]

2. Primary Outcome

Title	Progression Free Survival (PFS) in Participants Treated With Nivolumab Plus Chemotherapy vs Chemotherapy With PD-L1 CPS ≥ 5
Description	Progression Free Survival (PFS) is defined as the time from randomization to the date of the first documented PD or death due to any cause. PD is determined by blinded independent committee review (BICR) per RECIST1.1 criteria in participants treated with Nivolumab plus Chemotherapy vs Chemotherapy with PD-L1 CPS ≥ 5. Progressive disease (PD) is defined as at least a 20% increase in the sum of diameters of target lesions, taking in reference the smallest sum on study that also demonstrated an absolute increase of at least 5 mm. CPS is defined as the number of PD-L1 staining cells (tumor cells, lymphocytes, macrophages) divided by the total number of viable tumor cells, multiplied by 100.
Time Frame	From randomization to the date of the first documented progressive disease (PD) per BICR or death due to any cause (up to approximately 10 months)

Outcome Measure Data

Analysis Population Description

All randomized participants with PD-L1 CPS ≥ 5

Arm/Group Title	Arm 1: Nivolumab + Chemotherapy (XELOX or FOLFOX)	Arm 2a: Chemotherapy (XELOX or FOLFOX)
Arm/Group Description:	Nivolumab + Xelox: Nivolumab 360 mg IV over 30 minutes on Day 1 of each treatment cycle, every 3 weeks + Oxaliplatin 130 mg/m2 IV on Day 1 of each treatment cycle + capecitabine 1000 mg/m2 orally twice daily (ie, 1000 mg/m2 in the morning and 1000 mg/m2 in the evening) on Days 1 to 14 of each treatment cycle, every 3 weeks Nivolumab + Folfox: Nivolumab 240 mg IV over 30 minutes on Day 1 of each treatment cycle, every 2 weeks + Oxaliplatin 85 mg/m2 + leucovorin 400 mg/m2 + fluorouracil 400 mg/m2 IV on Day 1 of each treatment cycle, and fluorouracil 1200 mg/m2 IV continuous infusion over 24 hours (or per local standard) daily on Days 1 and 2 of each treatment cycle, every 2 weeks	Chemotherapy (XELOX or FOLFOX): Xelox: Oxaliplatin 130 mg/m2 IV on Day 1 of each treatment cycle + capecitabine 1000 mg/m2 orally twice daily (ie, 1000 mg/m2 in the morning and 1000 mg/m2 in the evening) on Days 1 to 14 of each treatment cycle, every 3 weeks. Folfox: Oxaliplatin 85 mg/m2 + leucovorin 400 mg/m2 + fluorouracil 400 mg/m2 IV on Day 1 of each treatment cycle, and fluorouracil 1200 mg/m2 IV continuous infusion over 24 hours (or per local standard) daily on Days 1 and 2 of each treatment cycle, every 2 weeks. Comparison group to Arm 1.
Overall Number of Participants Analyzed	473	482
Median (95% Confidence Interval); Unit of Measure: Months
	7.69; (7.03 to 9.17)	6.05; (5.55 to 6.90)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm 1: Nivolumab + Chemotherapy (XELOX or FOLFOX), Arm 2a: Chemotherapy (XELOX or FOLFOX)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.68
	Confidence Interval	(2-Sided) 98%; 0.56 to 0.81
	Estimation Comments	[Not Specified]

3. Secondary Outcome

Title	OS in Participants Treated With Nivolumab Plus Chemotherapy vs Chemotherapy
Description	Overall survival (OS), defined as the time from randomization to the time of death, in participants treated with Nivolumab plus Chemotherapy vs Chemotherapy with PD-L1 CPS ≥ 1, 10, and all randomized participants. CPS is defined as the number of PD-L1 staining cells (tumor cells, lymphocytes, macrophages) divided by the total number of viable tumor cells, multiplied by 100.
Time Frame	From the date of randomization up to the date of death, up to approximately 17 months

Outcome Measure Data

Analysis Population Description

All randomized participants with available measurements in various subsets as determined by PD-L1 CPS status

Arm/Group Title		Arm 1: Nivolumab + Chemotherapy (XELOX or FOLFOX)	Arm 2a: Chemotherapy (XELOX or FOLFOX)
Arm/Group Description:		Nivolumab + Xelox: Nivolumab 360 mg IV over 30 minutes on Day 1 of each treatment cycle, every 3 weeks + Oxaliplatin 130 mg/m2 IV on Day 1 of each treatment cycle + capecitabine 1000 mg/m2 orally twice daily (ie, 1000 mg/m2 in the morning and 1000 mg/m2 in the evening) on Days 1 to 14 of each treatment cycle, every 3 weeks Nivolumab + Folfox: Nivolumab 240 mg IV over 30 minutes on Day 1 of each treatment cycle, every 2 weeks + Oxaliplatin 85 mg/m2 + leucovorin 400 mg/m2 + fluorouracil 400 mg/m2 IV on Day 1 of each treatment cycle, and fluorouracil 1200 mg/m2 IV continuous infusion over 24 hours (or per local standard) daily on Days 1 and 2 of each treatment cycle, every 2 weeks	Chemotherapy (XELOX or FOLFOX): Xelox: Oxaliplatin 130 mg/m2 IV on Day 1 of each treatment cycle + capecitabine 1000 mg/m2 orally twice daily (ie, 1000 mg/m2 in the morning and 1000 mg/m2 in the evening) on Days 1 to 14 of each treatment cycle, every 3 weeks. Folfox: Oxaliplatin 85 mg/m2 + leucovorin 400 mg/m2 + fluorouracil 400 mg/m2 IV on Day 1 of each treatment cycle, and fluorouracil 1200 mg/m2 IV continuous infusion over 24 hours (or per local standard) daily on Days 1 and 2 of each treatment cycle, every 2 weeks. Comparison group to Arm 1.
Overall Number of Participants Analyzed		789	792
Median (95% Confidence Interval); Unit of Measure: Months
All randomized participants	Number Analyzed	789 participants	792 participants
		13.83; (12.55 to 14.55)	11.56; (10.87 to 12.48)
Participants with CPS ≥ 1	Number Analyzed	641 participants	655 participants
		13.96; (12.55 to 14.98)	11.33; (10.64 to 12.25)
Participants with PD-L1 CPS ≥ 10	Number Analyzed	375 participants	393 participants
		15.01; (13.77 to 16.79)	10.87; (9.82 to 11.83)

4. Secondary Outcome

Title	PFS in Participants Treated With Nivolumab Plus Chemotherapy vs Chemotherapy
Description	Progression free survival (PFS), defined as the time from randomization to the date of the first documented progressive disease (PD) or death due to any cause, in participants treated with Nivolumab plus Chemotherapy vs Chemotherapy by BICR per RECIST1.1 in participants with PD-L1 CPS ≥ 10, 1, or all randomized subjects. Progreessive disease (PD) is defined as at least a 20% increase in the sum of diameters of target lesions, taking in reference the smallest sum on study that also demonstrated an absolute increase of at least 5 mm. CPS is defined as the number of PD-L1 staining cells (tumor cells, lymphocytes, macrophages) divided by the total number of viable tumor cells, multiplied by 100.
Time Frame	From randomization to the date of the first documented progressive disease (PD) per BICR or death due to any cause (up to approximately 10 months)

Outcome Measure Data

Analysis Population Description

All randomized participants with available measurements in various subsets as determined by PD-L1 CPS status

Arm/Group Title		Arm 1: Nivolumab + Chemotherapy (XELOX or FOLFOX)	Arm 2a: Chemotherapy (XELOX or FOLFOX)
Arm/Group Description:		Nivolumab + Xelox: Nivolumab 360 mg IV over 30 minutes on Day 1 of each treatment cycle, every 3 weeks + Oxaliplatin 130 mg/m2 IV on Day 1 of each treatment cycle + capecitabine 1000 mg/m2 orally twice daily (ie, 1000 mg/m2 in the morning and 1000 mg/m2 in the evening) on Days 1 to 14 of each treatment cycle, every 3 weeks Nivolumab + Folfox: Nivolumab 240 mg IV over 30 minutes on Day 1 of each treatment cycle, every 2 weeks + Oxaliplatin 85 mg/m2 + leucovorin 400 mg/m2 + fluorouracil 400 mg/m2 IV on Day 1 of each treatment cycle, and fluorouracil 1200 mg/m2 IV continuous infusion over 24 hours (or per local standard) daily on Days 1 and 2 of each treatment cycle, every 2 weeks	Chemotherapy (XELOX or FOLFOX): Xelox: Oxaliplatin 130 mg/m2 IV on Day 1 of each treatment cycle + capecitabine 1000 mg/m2 orally twice daily (ie, 1000 mg/m2 in the morning and 1000 mg/m2 in the evening) on Days 1 to 14 of each treatment cycle, every 3 weeks. Folfox: Oxaliplatin 85 mg/m2 + leucovorin 400 mg/m2 + fluorouracil 400 mg/m2 IV on Day 1 of each treatment cycle, and fluorouracil 1200 mg/m2 IV continuous infusion over 24 hours (or per local standard) daily on Days 1 and 2 of each treatment cycle, every 2 weeks. Comparison group to Arm 1.
Overall Number of Participants Analyzed		789	792
Median (95% Confidence Interval); Unit of Measure: Months
All randomized participants	Number Analyzed	789 participants	792 participants
		7.66; (7.10 to 8.54)	6.93; (6.60 to 7.13)
Participants with CPS ≥ 1	Number Analyzed	641 participants	655 participants
		7.49; (7.03 to 8.41)	6.90; (6.08 to 7.03)
Participants with CPS ≥ 10	Number Analyzed	375 participants	393 participants
		8.31; (6.97 to 9.69)	5.78; (5.45 to 6.87)

5. Secondary Outcome

Title	Objective Response Rate
Description	Objective response rate (ORR) as assessed by BICR in participants with PD-L1 CPS ≥ 10, 5, 1, or all randomized participants. ORR is a percentage of participants determined by the number of participants with a best overall response (BOR) of complete response (CR) or partial response (PR) divided by the number of measurable participants with target lesion at baseline. BOR is defined as the best response designation as determined by the BICR, recorded between the date of randomization and the date of objectively documented progression (per RECIST 1.1 as determined by the BICR) or the date of subsequent anti-cancer therapy, whichever occurs first. CR is defined as the disappearance of all target lesions. PR is define as at 30% decrease in the sum of diameters of target lesions. The 806 chemotherapy treated participants are split into two separate arms (Arm 2a and Arm 2b) to act as comparison groups to the other treatment arms.
Time Frame	From randomization to the date of objectively documented progression or the date of subsequent anti-cancer therapy, whichever occurs first (up to approximately 43 months)

Outcome Measure Data

Analysis Population Description

All randomized participants in various subsets as determined by PD-L1 CPS status

Arm/Group Title		Arm 1: Nivolumab + Chemotherapy (XELOX or FOLFOX)	Arm 2a: Chemotherapy (XELOX or FOLFOX)	Arm 2b: Chemotherapy (XELOX or FOLFOX)	Arm 3: Nivolumab + Ipilimumab
Arm/Group Description:		Nivolumab + Xelox: Nivolumab 360 mg IV over 30 minutes on Day 1 of each treatment cycle, every 3 weeks + Oxaliplatin 130 mg/m2 IV on Day 1 of each treatment cycle + capecitabine 1000 mg/m2 orally twice daily (ie, 1000 mg/m2 in the morning and 1000 mg/m2 in the evening) on Days 1 to 14 of each treatment cycle, every 3 weeks Nivolumab + Folfox: Nivolumab 240 mg IV over 30 minutes on Day 1 of each treatment cycle, every 2 weeks + Oxaliplatin 85 mg/m2 + leucovorin 400 mg/m2 + fluorouracil 400 mg/m2 IV on Day 1 of each treatment cycle, and fluorouracil 1200 mg/m2 IV continuous infusion over 24 hours (or per local standard) daily on Days 1 and 2 of each treatment cycle, every 2 weeks	Chemotherapy (XELOX or FOLFOX): Xelox: Oxaliplatin 130 mg/m2 IV on Day 1 of each treatment cycle + capecitabine 1000 mg/m2 orally twice daily (ie, 1000 mg/m2 in the morning and 1000 mg/m2 in the evening) on Days 1 to 14 of each treatment cycle, every 3 weeks. Folfox: Oxaliplatin 85 mg/m2 + leucovorin 400 mg/m2 + fluorouracil 400 mg/m2 IV on Day 1 of each treatment cycle, and fluorouracil 1200 mg/m2 IV continuous infusion over 24 hours (or per local standard) daily on Days 1 and 2 of each treatment cycle, every 2 weeks. This arm is a subgroup of the chemotherapy group that acts as a comparison group to Arm 1.	Chemotherapy (XELOX or FOLFOX): Xelox: Oxaliplatin 130 mg/m2 IV on Day 1 of each treatment cycle + capecitabine 1000 mg/m2 orally twice daily (ie, 1000 mg/m2 in the morning and 1000 mg/m2 in the evening) on Days 1 to 14 of each treatment cycle, every 3 weeks. Folfox: Oxaliplatin 85 mg/m2 + leucovorin 400 mg/m2 + fluorouracil 400 mg/m2 IV on Day 1 of each treatment cycle, and fluorouracil 1200 mg/m2 IV continuous infusion over 24 hours (or per local standard) daily on Days 1 and 2 of each treatment cycle, every 2 weeks. This arm is a subgroup of the chemotherapy group that acts as a comparison group to Arm 3.	1 mg/kg nivolumab administered IV over 30 minutes followed by ipilimumab 3 mg/kg administered IV over 30 minutes on Day 1 of each treatment cycle every 3 weeks for 4 doses (Cycles 1 to 4), followed by nivolumab 240 mg administered IV over 30 minutes on Day 1 of each treatment cycle every 2 weeks (Cycle 5 and beyond). Arm is closed to enrollment as of 05-June-2018.
Overall Number of Participants Analyzed		789	792	404	409
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of Participants
Participants with CPS ≥ 1	Number Analyzed	504 participants	515 participants	319 participants	322 participants
		59.5; (55 to 64)	46.4; (42 to 51)	37.3; (32.0 to 42.9)	21.7; (17.4 to 26.6)
Participants with CPS ≥ 5	Number Analyzed	378 participants	391 participants	239 participants	234 participants
		59.8; (55 to 65)	45.3; (40 to 50)	37.7; (31.5 to 44.1)	23.1; (17.8 to 29.0)
Participants with CPS ≥ 10	Number Analyzed	300 participants	319 participants	198 participants	181 participants
		58.3; (53 to 64)	44.2; (39 to 50)	35.9; (29.2 to 43.0)	24.3; (18.3 to 31.2)
All randomized participants	Number Analyzed	789 participants	792 participants	404 participants	409 participants
		46.9; (43.4 to 50.4)	37.0; (33.6 to 40.5)	34.9; (30.3 to 39.8)	20.8; (17.0 to 25.0)

6. Secondary Outcome

Title	OS in Participants Treated With Nivolumab Plus Ipilimumab vs Chemotherapy
Description	Overall survival (OS), defined as the time from randomization to the time of death, in participants treated with Nivolumab plus Ipilimumab vs Chemotherapy with PD-L1 CPS (combined positive score) ≥ 1, 5, 10, and all randomized participants. CPS is defined as the number of PD-L1 staining cells (tumor cells, lymphocytes, macrophages) divided by the total number of viable tumor cells, multiplied by 100.
Time Frame	From the date of randomization up to the date of death, up to approximately 14 months

Outcome Measure Data

Analysis Population Description

All randomized participants with available measurements in various subsets as determined by PD-L1 CPS status

Arm/Group Title		Arm 2b: Chemotherapy (XELOX or FOLFOX)	Arm 3: Nivolumab + Ipilimumab
Arm/Group Description:		Chemotherapy (XELOX or FOLFOX): Xelox: Oxaliplatin 130 mg/m2 IV on Day 1 of each treatment cycle + capecitabine 1000 mg/m2 orally twice daily (ie, 1000 mg/m2 in the morning and 1000 mg/m2 in the evening) on Days 1 to 14 of each treatment cycle, every 3 weeks. Folfox: Oxaliplatin 85 mg/m2 + leucovorin 400 mg/m2 + fluorouracil 400 mg/m2 IV on Day 1 of each treatment cycle, and fluorouracil 1200 mg/m2 IV continuous infusion over 24 hours (or per local standard) daily on Days 1 and 2 of each treatment cycle, every 2 weeks. Comparison group to Arm 3.	1 mg/kg nivolumab administered IV over 30 minutes followed by ipilimumab 3 mg/kg administered IV over 30 minutes on Day 1 of each treatment cycle every 3 weeks for 4 doses (Cycles 1 to 4), followed by nivolumab 240 mg administered IV over 30 minutes on Day 1 of each treatment cycle every 2 weeks (Cycle 5 and beyond). Arm is closed to enrollment as of 05-June-2018.
Overall Number of Participants Analyzed		404	409
Median (95% Confidence Interval); Unit of Measure: Months
All randomized participants	Number Analyzed	404 participants	409 participants
		11.83; (10.97 to 12.71)	11.73; (9.56 to 13.54)
Participants with CPS ≥ 1	Number Analyzed	319 participants	322 participants
		11.47; (10.48 to 12.65)	11.73; (9.49 to 13.54)
Participants with CPS ≥ 5	Number Analyzed	239 participants	234 participants
		11.63; (10.05 to 12.71)	11.24; (9.17 to 13.40)
Participants with CPS ≥ 10	Number Analyzed	198 participants	181 participants
		11.33; (9.92 to 12.65)	11.63; (9.26 to 13.54)

7. Secondary Outcome

Title	Time to Symptom Deterioration (TTSD)
Description	TTSD is defined as the the time from randomization until a clinically meaningful decline from baseline in Gastric Cancer Subscale (GaCS) score. A clinically meaningful deterioration is defined as a reduction of 8.2 points in the GaCS score. Subjects who do not deteriorate will be censored at the time of their last GACS assessment. Subjects without baseline GaCS assessment will be censored on the randomization date. Those with baseline GaCS, who do not have any GaCS assessments after randomization will be censored on the day after randomization.
Time Frame	From randomization until a clinically meaningful decline from baseline in GaCS score

Outcome Measure Data Not Reported

8. Secondary Outcome

Title	PFS in Participants Treated With Nivolumab Plus Ipilimumab vs Chemotherapy
Description	Progression Free Survival (PFS) is defined as the time from randomization to the date of the first documented PD or death due to any cause. PD is determined by blinded independent committee review (BICR) per RECIST1.1 criteria in participants treated with Nivolumab plus Ipilumab vs Chemotherapy with PD-L1 CPS ≥ 10, 5, 1 or all randomized participants. Progressive disease (PD) is defined as at least a 20% increase in the sum of diameters of target lesions, taking in reference the smallest sum on study that also demonstrated an absolute increase of at least 5 mm. CPS is defined as the number of PD-L1 staining cells (tumor cells, lymphocytes, macrophages) divided by the total number of viable tumor cells, multiplied by 100.
Time Frame	From randomization to the date of the first documented progressive disease (PD) per BICR or death due to any cause (up to approximately 9 months)

Outcome Measure Data

Analysis Population Description

All randomized participants with available measurements in various subsets as determined by PD-L1 CPS status

Arm/Group Title		Arm 2b: Chemotherapy (XELOX or FOLFOX)	Arm 3: Nivolumab + Ipilimumab
Arm/Group Description:		Chemotherapy (XELOX or FOLFOX): Xelox: Oxaliplatin 130 mg/m2 IV on Day 1 of each treatment cycle + capecitabine 1000 mg/m2 orally twice daily (ie, 1000 mg/m2 in the morning and 1000 mg/m2 in the evening) on Days 1 to 14 of each treatment cycle, every 3 weeks. Folfox: Oxaliplatin 85 mg/m2 + leucovorin 400 mg/m2 + fluorouracil 400 mg/m2 IV on Day 1 of each treatment cycle, and fluorouracil 1200 mg/m2 IV continuous infusion over 24 hours (or per local standard) daily on Days 1 and 2 of each treatment cycle, every 2 weeks. Comparison group to Arm 3.	1 mg/kg nivolumab administered IV over 30 minutes followed by ipilimumab 3 mg/kg administered IV over 30 minutes on Day 1 of each treatment cycle every 3 weeks for 4 doses (Cycles 1 to 4), followed by nivolumab 240 mg administered IV over 30 minutes on Day 1 of each treatment cycle every 2 weeks (Cycle 5 and beyond). Arm is closed to enrollment as of 05-June-2018.
Overall Number of Participants Analyzed		404	409
Median (95% Confidence Interval); Unit of Measure: Months
All randomized participants	Number Analyzed	404 participants	409 participants
		7.06; (6.87 to 8.21)	2.83; (2.63 to 3.58)
PD-L1 CPS ≥ 1	Number Analyzed	319 participants	322 participants
		6.93; (5.98 to 7.26)	2.79; (2.60 to 3.91)
PD-L1 CPS ≥ 5	Number Analyzed	239 participants	234 participants
		6.28; (5.59 to 7.06)	2.83; (2.60 to 4.04)
PD-L1 CPS ≥ 10	Number Analyzed	198 participants	181 participants
		6.28; (5.52 to 7.13)	2.89; (2.63 to 4.24)

Adverse Events

Time Frame	All-cause mortality was assessed from date of randomization to study completion (up to approximately 42 months). Serious Adverse events and other adverse events were assessed from date of first dose to 100 days following date of last dose (up to approximately 38 months).
Adverse Event Reporting Description	All-Cause Mortality =all randomized participants AEs and NSAEs (Other Adverse Events) = all treated participants
Arm/Group Title	Arm A: Nivolumab + Chemotherapy (XELOX or FOLFOX)	Arm B: Chemotherapy (XELOX or FOLFOX)	Arm C: Nivolumab + Ipilimumab
Arm/Group Description	Nivolumab + Xelox: Nivolumab 360 mg IV over 30 minutes on Day 1 of each treatment cycle, every 3 weeks + Oxaliplatin 130 mg/m2 IV on Day 1 of each treatment cycle + capecitabine 1000 mg/m2 orally twice daily (ie, 1000 mg/m2 in the morning and 1000 mg/m2 in the evening) on Days 1 to 14 of each treatment cycle, every 3 weeks Nivolumab + Folfox: Nivolumab 240 mg IV over 30 minutes on Day 1 of each treatment cycle, every 2 weeks + Oxaliplatin 85 mg/m2 + leucovorin 400 mg/m2 + fluorouracil 400 mg/m2 IV on Day 1 of each treatment cycle, and fluorouracil 1200 mg/m2 IV continuous infusion over 24 hours (or per local standard) daily on Days 1 and 2 of each treatment cycle, every 2 weeks	Chemotherapy (XELOX or FOLFOX): Xelox: Oxaliplatin 130 mg/m2 IV on Day 1 of each treatment cycle + capecitabine 1000 mg/m2 orally twice daily (ie, 1000 mg/m2 in the morning and 1000 mg/m2 in the evening) on Days 1 to 14 of each treatment cycle, every 3 weeks. Folfox: Oxaliplatin 85 mg/m2 + leucovorin 400 mg/m2 + fluorouracil 400 mg/m2 IV on Day 1 of each treatment cycle, and fluorouracil 1200 mg/m2 IV continuous infusion over 24 hours (or per local standard) daily on Days 1 and 2 of each treatment cycle, every 2 weeks. This chemotherapy group consists of the two comparison chemotherapy sub-groups. Arm 2a (792 participants) is the comparison group to Arm 1 and Arm 2b (404 participants) is the comparison group to Arm 3. Some participants were counted in both Arm 2a and Arm 2b.	1 mg/kg nivolumab administered IV over 30 minutes followed by ipilimumab 3 mg/kg administered IV over 30 minutes on Day 1 of each treatment cycle every 3 weeks for 4 doses (Cycles 1 to 4), followed by nivolumab 240 mg administered IV over 30 minutes on Day 1 of each treatment cycle every 2 weeks (Cycle 5 and beyond). Arm is closed to enrollment as of 05-June-2018.
All-Cause Mortality
	Arm A: Nivolumab + Chemotherapy (XELOX or FOLFOX)	Arm B: Chemotherapy (XELOX or FOLFOX)	Arm C: Nivolumab + Ipilimumab
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	626/789 (79.34%)	694/833 (83.31%)	346/409 (84.60%)
Serious Adverse Events
	Arm A: Nivolumab + Chemotherapy (XELOX or FOLFOX)	Arm B: Chemotherapy (XELOX or FOLFOX)	Arm C: Nivolumab + Ipilimumab
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	529/782 (67.65%)	472/806 (58.56%)	307/403 (76.18%)
Blood and lymphatic system disorders
Anaemia † 1	28/782 (3.58%)	17/806 (2.11%)	13/403 (3.23%)
Blood loss anaemia † 1	0/782 (0.00%)	1/806 (0.12%)	0/403 (0.00%)
Bone marrow failure † 1	1/782 (0.13%)	0/806 (0.00%)	0/403 (0.00%)
Disseminated intravascular coagulation † 1	1/782 (0.13%)	0/806 (0.00%)	0/403 (0.00%)
Febrile bone marrow aplasia † 1	2/782 (0.26%)	0/806 (0.00%)	1/403 (0.25%)
Febrile neutropenia † 1	20/782 (2.56%)	10/806 (1.24%)	1/403 (0.25%)
Immune thrombocytopenia † 1	1/782 (0.13%)	1/806 (0.12%)	0/403 (0.00%)
Leukocytosis † 1	0/782 (0.00%)	0/806 (0.00%)	1/403 (0.25%)
Leukopenia † 1	0/782 (0.00%)	2/806 (0.25%)	0/403 (0.00%)
Lymphadenopathy † 1	1/782 (0.13%)	0/806 (0.00%)	0/403 (0.00%)
Myelosuppression † 1	4/782 (0.51%)	2/806 (0.25%)	0/403 (0.00%)
Neutropenia † 1	4/782 (0.51%)	3/806 (0.37%)	0/403 (0.00%)
Pancytopenia † 1	1/782 (0.13%)	1/806 (0.12%)	0/403 (0.00%)
Splenic haematoma † 1	1/782 (0.13%)	0/806 (0.00%)	0/403 (0.00%)
Thrombocytopenia † 1	4/782 (0.51%)	2/806 (0.25%)	2/403 (0.50%)
Thrombotic microangiopathy † 1	0/782 (0.00%)	1/806 (0.12%)	0/403 (0.00%)
Cardiac disorders
Acute coronary syndrome † 1	1/782 (0.13%)	1/806 (0.12%)	0/403 (0.00%)
Acute myocardial infarction † 1	4/782 (0.51%)	3/806 (0.37%)	1/403 (0.25%)
Angina pectoris † 1	1/782 (0.13%)	1/806 (0.12%)	0/403 (0.00%)
Angina unstable † 1	1/782 (0.13%)	0/806 (0.00%)	0/403 (0.00%)
Arrhythmia † 1	1/782 (0.13%)	1/806 (0.12%)	0/403 (0.00%)
Atrial fibrillation † 1	0/782 (0.00%)	1/806 (0.12%)	1/403 (0.25%)
Atrioventricular block complete † 1	1/782 (0.13%)	0/806 (0.00%)	0/403 (0.00%)
Autoimmune myocarditis † 1	1/782 (0.13%)	0/806 (0.00%)	0/403 (0.00%)
Cardiac arrest † 1	2/782 (0.26%)	1/806 (0.12%)	1/403 (0.25%)
Cardiac failure † 1	0/782 (0.00%)	2/806 (0.25%)	2/403 (0.50%)
Cardiac failure acute † 1	0/782 (0.00%)	1/806 (0.12%)	0/403 (0.00%)
Cardiac failure congestive † 1	1/782 (0.13%)	1/806 (0.12%)	0/403 (0.00%)
Cardiac tamponade † 1	1/782 (0.13%)	2/806 (0.25%)	0/403 (0.00%)
Cardio-respiratory arrest † 1	2/782 (0.26%)	2/806 (0.25%)	2/403 (0.50%)
Myocardial infarction † 1	2/782 (0.26%)	5/806 (0.62%)	3/403 (0.74%)
Myocarditis † 1	0/782 (0.00%)	0/806 (0.00%)	1/403 (0.25%)
Pericardial effusion † 1	3/782 (0.38%)	3/806 (0.37%)	1/403 (0.25%)
Supraventricular extrasystoles † 1	0/782 (0.00%)	0/806 (0.00%)	1/403 (0.25%)
Supraventricular tachycardia † 1	1/782 (0.13%)	1/806 (0.12%)	0/403 (0.00%)
Tachyarrhythmia † 1	0/782 (0.00%)	0/806 (0.00%)	1/403 (0.25%)
Tachycardia † 1	1/782 (0.13%)	1/806 (0.12%)	0/403 (0.00%)
Congenital, familial and genetic disorders
Choledochal cyst † 1	0/782 (0.00%)	1/806 (0.12%)	0/403 (0.00%)
Microvillous inclusion disease † 1	0/782 (0.00%)	0/806 (0.00%)	1/403 (0.25%)
Pyloric stenosis † 1	3/782 (0.38%)	1/806 (0.12%)	1/403 (0.25%)
Tracheo-oesophageal fistula † 1	0/782 (0.00%)	0/806 (0.00%)	1/403 (0.25%)
Ear and labyrinth disorders
Vertigo † 1	1/782 (0.13%)	0/806 (0.00%)	0/403 (0.00%)
Endocrine disorders
Adrenal insufficiency † 1	3/782 (0.38%)	1/806 (0.12%)	4/403 (0.99%)
Autoimmune thyroiditis † 1	0/782 (0.00%)	0/806 (0.00%)	1/403 (0.25%)
Hyperthyroidism † 1	0/782 (0.00%)	0/806 (0.00%)	1/403 (0.25%)
Hypophysitis † 1	1/782 (0.13%)	0/806 (0.00%)	4/403 (0.99%)
Hypopituitarism † 1	3/782 (0.38%)	0/806 (0.00%)	1/403 (0.25%)
Hypothalamo-pituitary disorder † 1	1/782 (0.13%)	0/806 (0.00%)	1/403 (0.25%)
Hypothyroidism † 1	1/782 (0.13%)	0/806 (0.00%)	1/403 (0.25%)
Immune-mediated hypophysitis † 1	0/782 (0.00%)	0/806 (0.00%)	1/403 (0.25%)
Inappropriate antidiuretic hormone secretion † 1	1/782 (0.13%)	0/806 (0.00%)	0/403 (0.00%)
Secondary adrenocortical insufficiency † 1	0/782 (0.00%)	0/806 (0.00%)	1/403 (0.25%)
Thyroiditis † 1	0/782 (0.00%)	0/806 (0.00%)	1/403 (0.25%)
Eye disorders
Cataract † 1	1/782 (0.13%)	0/806 (0.00%)	0/403 (0.00%)
Ocular vasculitis † 1	0/782 (0.00%)	0/806 (0.00%)	1/403 (0.25%)
Visual impairment † 1	1/782 (0.13%)	0/806 (0.00%)	0/403 (0.00%)
Gastrointestinal disorders
Abdominal adhesions † 1	0/782 (0.00%)	1/806 (0.12%)	0/403 (0.00%)
Abdominal distension † 1	1/782 (0.13%)	1/806 (0.12%)	1/403 (0.25%)
Abdominal hernia † 1	0/782 (0.00%)	1/806 (0.12%)	0/403 (0.00%)
Abdominal pain † 1	12/782 (1.53%)	13/806 (1.61%)	4/403 (0.99%)
Abdominal pain lower † 1	0/782 (0.00%)	1/806 (0.12%)	0/403 (0.00%)
Abdominal pain upper † 1	2/782 (0.26%)	1/806 (0.12%)	2/403 (0.50%)
Ascites † 1	15/782 (1.92%)	9/806 (1.12%)	6/403 (1.49%)
Autoimmune colitis † 1	2/782 (0.26%)	0/806 (0.00%)	3/403 (0.74%)
Colitis † 1	6/782 (0.77%)	0/806 (0.00%)	11/403 (2.73%)
Constipation † 1	3/782 (0.38%)	3/806 (0.37%)	2/403 (0.50%)
Cyclic vomiting syndrome † 1	1/782 (0.13%)	1/806 (0.12%)	0/403 (0.00%)
Diarrhoea † 1	21/782 (2.69%)	14/806 (1.74%)	13/403 (3.23%)
Diverticulum intestinal haemorrhagic † 1	0/782 (0.00%)	1/806 (0.12%)	0/403 (0.00%)
Duodenal obstruction † 1	0/782 (0.00%)	0/806 (0.00%)	1/403 (0.25%)
Duodenal perforation † 1	0/782 (0.00%)	0/806 (0.00%)	1/403 (0.25%)
Dyspepsia † 1	0/782 (0.00%)	0/806 (0.00%)	2/403 (0.50%)
Dysphagia † 1	13/782 (1.66%)	23/806 (2.85%)	9/403 (2.23%)
Enteritis † 1	1/782 (0.13%)	0/806 (0.00%)	2/403 (0.50%)
Enterocolitis † 1	4/782 (0.51%)	0/806 (0.00%)	0/403 (0.00%)
Gastric haemorrhage † 1	3/782 (0.38%)	11/806 (1.36%)	4/403 (0.99%)
Gastric perforation † 1	1/782 (0.13%)	3/806 (0.37%)	1/403 (0.25%)
Gastric stenosis † 1	0/782 (0.00%)	1/806 (0.12%)	0/403 (0.00%)
Gastric ulcer † 1	0/782 (0.00%)	2/806 (0.25%)	0/403 (0.00%)
Gastrointestinal fistula † 1	1/782 (0.13%)	0/806 (0.00%)	1/403 (0.25%)
Gastrointestinal haemorrhage † 1	13/782 (1.66%)	9/806 (1.12%)	4/403 (0.99%)
Gastrointestinal inflammation † 1	1/782 (0.13%)	1/806 (0.12%)	0/403 (0.00%)
Gastrointestinal necrosis † 1	0/782 (0.00%)	1/806 (0.12%)	0/403 (0.00%)
Gastrointestinal obstruction † 1	1/782 (0.13%)	0/806 (0.00%)	1/403 (0.25%)
Gastrointestinal perforation † 1	0/782 (0.00%)	1/806 (0.12%)	0/403 (0.00%)
Gastrointestinal stenosis † 1	1/782 (0.13%)	2/806 (0.25%)	0/403 (0.00%)
Gastrooesophageal reflux disease † 1	0/782 (0.00%)	0/806 (0.00%)	1/403 (0.25%)
Haematemesis † 1	1/782 (0.13%)	2/806 (0.25%)	1/403 (0.25%)
Haematochezia † 1	0/782 (0.00%)	1/806 (0.12%)	0/403 (0.00%)
Haemoperitoneum † 1	0/782 (0.00%)	1/806 (0.12%)	0/403 (0.00%)
Ileus † 1	4/782 (0.51%)	2/806 (0.25%)	1/403 (0.25%)
Ileus paralytic † 1	0/782 (0.00%)	2/806 (0.25%)	0/403 (0.00%)
Immune-mediated enterocolitis † 1	1/782 (0.13%)	1/806 (0.12%)	11/403 (2.73%)
Impaired gastric emptying † 1	0/782 (0.00%)	2/806 (0.25%)	1/403 (0.25%)
Intestinal haemorrhage † 1	0/782 (0.00%)	1/806 (0.12%)	0/403 (0.00%)
Intestinal obstruction † 1	3/782 (0.38%)	6/806 (0.74%)	2/403 (0.50%)
Intestinal perforation † 1	2/782 (0.26%)	2/806 (0.25%)	0/403 (0.00%)
Intestinal stenosis † 1	0/782 (0.00%)	1/806 (0.12%)	0/403 (0.00%)
Large intestinal haemorrhage † 1	0/782 (0.00%)	0/806 (0.00%)	1/403 (0.25%)
Large intestinal stenosis † 1	1/782 (0.13%)	0/806 (0.00%)	0/403 (0.00%)
Large intestine perforation † 1	0/782 (0.00%)	0/806 (0.00%)	2/403 (0.50%)
Lower gastrointestinal haemorrhage † 1	1/782 (0.13%)	1/806 (0.12%)	0/403 (0.00%)
Malabsorption † 1	1/782 (0.13%)	0/806 (0.00%)	1/403 (0.25%)
Malignant gastrointestinal obstruction † 1	1/782 (0.13%)	0/806 (0.00%)	0/403 (0.00%)
Melaena † 1	2/782 (0.26%)	0/806 (0.00%)	0/403 (0.00%)
Nausea † 1	8/782 (1.02%)	10/806 (1.24%)	7/403 (1.74%)
Obstruction gastric † 1	2/782 (0.26%)	5/806 (0.62%)	5/403 (1.24%)
Obstructive pancreatitis † 1	0/782 (0.00%)	0/806 (0.00%)	2/403 (0.50%)
Oesophageal compression † 1	0/782 (0.00%)	1/806 (0.12%)	0/403 (0.00%)
Oesophageal fistula † 1	1/782 (0.13%)	0/806 (0.00%)	0/403 (0.00%)
Oesophageal haemorrhage † 1	1/782 (0.13%)	1/806 (0.12%)	1/403 (0.25%)
Oesophageal obstruction † 1	4/782 (0.51%)	3/806 (0.37%)	4/403 (0.99%)
Oesophageal pain † 1	1/782 (0.13%)	0/806 (0.00%)	0/403 (0.00%)
Oesophageal stenosis † 1	3/782 (0.38%)	0/806 (0.00%)	2/403 (0.50%)
Oesophageal ulcer haemorrhage † 1	0/782 (0.00%)	1/806 (0.12%)	0/403 (0.00%)
Oesophageal varices haemorrhage † 1	0/782 (0.00%)	1/806 (0.12%)	0/403 (0.00%)
Oesophagitis † 1	0/782 (0.00%)	1/806 (0.12%)	0/403 (0.00%)
Pancreatitis † 1	1/782 (0.13%)	0/806 (0.00%)	3/403 (0.74%)
Pancreatitis acute † 1	1/782 (0.13%)	1/806 (0.12%)	0/403 (0.00%)
Peritoneal adhesions † 1	0/782 (0.00%)	1/806 (0.12%)	0/403 (0.00%)
Prepyloric stenosis † 1	0/782 (0.00%)	1/806 (0.12%)	0/403 (0.00%)
Proctitis † 1	0/782 (0.00%)	0/806 (0.00%)	1/403 (0.25%)
Retroperitoneal haematoma † 1	0/782 (0.00%)	1/806 (0.12%)	0/403 (0.00%)
Small intestinal obstruction † 1	4/782 (0.51%)	5/806 (0.62%)	0/403 (0.00%)
Stomatitis † 1	1/782 (0.13%)	0/806 (0.00%)	0/403 (0.00%)
Subileus † 1	1/782 (0.13%)	0/806 (0.00%)	1/403 (0.25%)
Thrombosis mesenteric vessel † 1	1/782 (0.13%)	0/806 (0.00%)	1/403 (0.25%)
Upper gastrointestinal haemorrhage † 1	17/782 (2.17%)	10/806 (1.24%)	13/403 (3.23%)
Vomiting † 1	29/782 (3.71%)	24/806 (2.98%)	12/403 (2.98%)
General disorders
Asthenia † 1	1/782 (0.13%)	5/806 (0.62%)	3/403 (0.74%)
Catheter site extravasation † 1	1/782 (0.13%)	0/806 (0.00%)	0/403 (0.00%)
Catheter site haemorrhage † 1	1/782 (0.13%)	0/806 (0.00%)	0/403 (0.00%)
Chest discomfort † 1	0/782 (0.00%)	1/806 (0.12%)	0/403 (0.00%)
Complication associated with device † 1	1/782 (0.13%)	2/806 (0.25%)	1/403 (0.25%)
Death † 1	1/782 (0.13%)	1/806 (0.12%)	2/403 (0.50%)
Disease progression † 1	1/782 (0.13%)	4/806 (0.50%)	0/403 (0.00%)
Effusion † 1	1/782 (0.13%)	0/806 (0.00%)	0/403 (0.00%)
Euthanasia † 1	0/782 (0.00%)	1/806 (0.12%)	0/403 (0.00%)
Face oedema † 1	0/782 (0.00%)	1/806 (0.12%)	0/403 (0.00%)
Fatigue † 1	3/782 (0.38%)	2/806 (0.25%)	6/403 (1.49%)
Gait disturbance † 1	0/782 (0.00%)	1/806 (0.12%)	0/403 (0.00%)
General physical health deterioration † 1	5/782 (0.64%)	7/806 (0.87%)	3/403 (0.74%)
Generalised oedema † 1	0/782 (0.00%)	0/806 (0.00%)	1/403 (0.25%)
Inflammation † 1	0/782 (0.00%)	1/806 (0.12%)	0/403 (0.00%)
Malaise † 1	0/782 (0.00%)	3/806 (0.37%)	1/403 (0.25%)
Mucosal inflammation † 1	1/782 (0.13%)	1/806 (0.12%)	0/403 (0.00%)
Multiple organ dysfunction syndrome † 1	2/782 (0.26%)	0/806 (0.00%)	2/403 (0.50%)
Non-cardiac chest pain † 1	2/782 (0.26%)	1/806 (0.12%)	0/403 (0.00%)
Oedema peripheral † 1	3/782 (0.38%)	0/806 (0.00%)	1/403 (0.25%)
Pain † 1	3/782 (0.38%)	4/806 (0.50%)	0/403 (0.00%)
Performance status decreased † 1	0/782 (0.00%)	1/806 (0.12%)	0/403 (0.00%)
Peripheral swelling † 1	1/782 (0.13%)	1/806 (0.12%)	0/403 (0.00%)
Pyrexia † 1	22/782 (2.81%)	11/806 (1.36%)	9/403 (2.23%)
Sudden death † 1	2/782 (0.26%)	3/806 (0.37%)	2/403 (0.50%)
Systemic inflammatory response syndrome † 1	0/782 (0.00%)	0/806 (0.00%)	1/403 (0.25%)
Ulcer haemorrhage † 1	0/782 (0.00%)	0/806 (0.00%)	1/403 (0.25%)
Hepatobiliary disorders
Acute hepatic failure † 1	0/782 (0.00%)	0/806 (0.00%)	1/403 (0.25%)
Autoimmune hepatitis † 1	0/782 (0.00%)	0/806 (0.00%)	6/403 (1.49%)
Bile duct stenosis † 1	0/782 (0.00%)	1/806 (0.12%)	0/403 (0.00%)
Bile duct stone † 1	3/782 (0.38%)	0/806 (0.00%)	0/403 (0.00%)
Biliary obstruction † 1	0/782 (0.00%)	2/806 (0.25%)	1/403 (0.25%)
Cholangitis † 1	3/782 (0.38%)	1/806 (0.12%)	0/403 (0.00%)
Cholangitis acute † 1	1/782 (0.13%)	0/806 (0.00%)	0/403 (0.00%)
Cholecystitis † 1	5/782 (0.64%)	0/806 (0.00%)	1/403 (0.25%)
Cholecystitis acute † 1	2/782 (0.26%)	0/806 (0.00%)	0/403 (0.00%)
Cholecystitis chronic † 1	0/782 (0.00%)	1/806 (0.12%)	0/403 (0.00%)
Cholestasis † 1	0/782 (0.00%)	0/806 (0.00%)	1/403 (0.25%)
Drug-induced liver injury † 1	1/782 (0.13%)	0/806 (0.00%)	5/403 (1.24%)
Hepatic cyst ruptured † 1	1/782 (0.13%)	0/806 (0.00%)	0/403 (0.00%)
Hepatic failure † 1	1/782 (0.13%)	1/806 (0.12%)	0/403 (0.00%)
Hepatic function abnormal † 1	3/782 (0.38%)	2/806 (0.25%)	5/403 (1.24%)
Hepatitis † 1	1/782 (0.13%)	0/806 (0.00%)	5/403 (1.24%)
Hepatitis acute † 1	1/782 (0.13%)	0/806 (0.00%)	1/403 (0.25%)
Hepatitis toxic † 1	1/782 (0.13%)	0/806 (0.00%)	0/403 (0.00%)
Hepatorenal failure † 1	0/782 (0.00%)	0/806 (0.00%)	2/403 (0.50%)
Hepatotoxicity † 1	0/782 (0.00%)	0/806 (0.00%)	1/403 (0.25%)
Hyperbilirubinaemia † 1	0/782 (0.00%)	0/806 (0.00%)	1/403 (0.25%)
Hypertransaminasaemia † 1	0/782 (0.00%)	0/806 (0.00%)	1/403 (0.25%)
Immune-mediated hepatic disorder † 1	0/782 (0.00%)	0/806 (0.00%)	1/403 (0.25%)
Immune-mediated hepatitis † 1	3/782 (0.38%)	0/806 (0.00%)	3/403 (0.74%)
Jaundice † 1	1/782 (0.13%)	0/806 (0.00%)	0/403 (0.00%)
Jaundice cholestatic † 1	6/782 (0.77%)	3/806 (0.37%)	2/403 (0.50%)
Jaundice extrahepatic obstructive † 1	0/782 (0.00%)	1/806 (0.12%)	0/403 (0.00%)
Liver disorder † 1	2/782 (0.26%)	0/806 (0.00%)	1/403 (0.25%)
Liver injury † 1	0/782 (0.00%)	0/806 (0.00%)	3/403 (0.74%)
Portal hypertension † 1	1/782 (0.13%)	0/806 (0.00%)	0/403 (0.00%)
Immune system disorders
Anaphylactic reaction † 1	1/782 (0.13%)	1/806 (0.12%)	0/403 (0.00%)
Contrast media allergy † 1	0/782 (0.00%)	0/806 (0.00%)	1/403 (0.25%)
Drug hypersensitivity † 1	4/782 (0.51%)	1/806 (0.12%)	0/403 (0.00%)
Hypersensitivity † 1	1/782 (0.13%)	0/806 (0.00%)	0/403 (0.00%)
Infections and infestations
Abdominal abscess † 1	2/782 (0.26%)	0/806 (0.00%)	0/403 (0.00%)
Abdominal infection † 1	1/782 (0.13%)	0/806 (0.00%)	0/403 (0.00%)
Abdominal sepsis † 1	1/782 (0.13%)	0/806 (0.00%)	0/403 (0.00%)
Amoebic colitis † 1	0/782 (0.00%)	0/806 (0.00%)	1/403 (0.25%)
Anal abscess † 1	2/782 (0.26%)	0/806 (0.00%)	0/403 (0.00%)
Appendicitis † 1	0/782 (0.00%)	1/806 (0.12%)	0/403 (0.00%)
Appendicitis perforated † 1	0/782 (0.00%)	0/806 (0.00%)	1/403 (0.25%)
Arthritis bacterial † 1	1/782 (0.13%)	0/806 (0.00%)	0/403 (0.00%)
Asymptomatic COVID-19 † 1	1/782 (0.13%)	0/806 (0.00%)	0/403 (0.00%)
Bacteraemia † 1	4/782 (0.51%)	1/806 (0.12%)	3/403 (0.74%)
Biliary tract infection † 1	2/782 (0.26%)	0/806 (0.00%)	0/403 (0.00%)
Bronchitis † 1	2/782 (0.26%)	0/806 (0.00%)	0/403 (0.00%)
Bronchitis viral † 1	0/782 (0.00%)	1/806 (0.12%)	0/403 (0.00%)
COVID-19 pneumonia † 1	1/782 (0.13%)	1/806 (0.12%)	0/403 (0.00%)
Cellulitis † 1	1/782 (0.13%)	3/806 (0.37%)	2/403 (0.50%)
Chorioretinitis † 1	1/782 (0.13%)	0/806 (0.00%)	0/403 (0.00%)
Clostridium difficile colitis † 1	2/782 (0.26%)	0/806 (0.00%)	0/403 (0.00%)
Clostridium difficile infection † 1	0/782 (0.00%)	0/806 (0.00%)	1/403 (0.25%)
Cystitis † 1	1/782 (0.13%)	0/806 (0.00%)	0/403 (0.00%)
Dengue fever † 1	0/782 (0.00%)	1/806 (0.12%)	0/403 (0.00%)
Device related infection † 1	2/782 (0.26%)	2/806 (0.25%)	1/403 (0.25%)
Device related sepsis † 1	0/782 (0.00%)	1/806 (0.12%)	0/403 (0.00%)
Diarrhoea infectious † 1	0/782 (0.00%)	1/806 (0.12%)	0/403 (0.00%)
Diverticulitis † 1	1/782 (0.13%)	0/806 (0.00%)	1/403 (0.25%)
Encephalitis † 1	2/782 (0.26%)	0/806 (0.00%)	0/403 (0.00%)
Endocarditis † 1	1/782 (0.13%)	0/806 (0.00%)	0/403 (0.00%)
Endophthalmitis † 1	1/782 (0.13%)	0/806 (0.00%)	0/403 (0.00%)
Enteritis infectious † 1	1/782 (0.13%)	0/806 (0.00%)	0/403 (0.00%)
Enterocolitis infectious † 1	1/782 (0.13%)	0/806 (0.00%)	0/403 (0.00%)
Epididymitis † 1	1/782 (0.13%)	0/806 (0.00%)	0/403 (0.00%)
Febrile infection † 1	0/782 (0.00%)	1/806 (0.12%)	0/403 (0.00%)
Giardiasis † 1	0/782 (0.00%)	0/806 (0.00%)	1/403 (0.25%)
Hepatitis C † 1	0/782 (0.00%)	1/806 (0.12%)	0/403 (0.00%)
Herpes simplex reactivation † 1	0/782 (0.00%)	0/806 (0.00%)	1/403 (0.25%)
Herpes virus infection † 1	1/782 (0.13%)	0/806 (0.00%)	0/403 (0.00%)
Infection † 1	2/782 (0.26%)	1/806 (0.12%)	1/403 (0.25%)
Influenza † 1	0/782 (0.00%)	0/806 (0.00%)	1/403 (0.25%)
Intervertebral discitis † 1	0/782 (0.00%)	1/806 (0.12%)	0/403 (0.00%)
Large intestine infection † 1	1/782 (0.13%)	0/806 (0.00%)	0/403 (0.00%)
Localised infection † 1	1/782 (0.13%)	0/806 (0.00%)	0/403 (0.00%)
Lower respiratory tract infection † 1	1/782 (0.13%)	1/806 (0.12%)	2/403 (0.50%)
Lung abscess † 1	1/782 (0.13%)	0/806 (0.00%)	1/403 (0.25%)
Lymphangitis † 1	0/782 (0.00%)	1/806 (0.12%)	0/403 (0.00%)
Mycobacterium avium complex infection † 1	1/782 (0.13%)	0/806 (0.00%)	0/403 (0.00%)
Neutropenic infection † 1	0/782 (0.00%)	1/806 (0.12%)	0/403 (0.00%)
Neutropenic sepsis † 1	1/782 (0.13%)	0/806 (0.00%)	0/403 (0.00%)
Oesophageal candidiasis † 1	1/782 (0.13%)	0/806 (0.00%)	0/403 (0.00%)
Osteomyelitis † 1	0/782 (0.00%)	1/806 (0.12%)	0/403 (0.00%)
Parainfluenzae virus infection † 1	0/782 (0.00%)	0/806 (0.00%)	1/403 (0.25%)
Peritonitis † 1	1/782 (0.13%)	1/806 (0.12%)	1/403 (0.25%)
Peritonitis bacterial † 1	3/782 (0.38%)	1/806 (0.12%)	0/403 (0.00%)
Pneumonia † 1	30/782 (3.84%)	21/806 (2.61%)	13/403 (3.23%)
Pneumonia bacterial † 1	1/782 (0.13%)	0/806 (0.00%)	0/403 (0.00%)
Pneumonia klebsiella † 1	1/782 (0.13%)	0/806 (0.00%)	0/403 (0.00%)
Pneumonia pneumococcal † 1	0/782 (0.00%)	1/806 (0.12%)	0/403 (0.00%)
Pneumonia viral † 1	0/782 (0.00%)	1/806 (0.12%)	0/403 (0.00%)
Psoas abscess † 1	0/782 (0.00%)	1/806 (0.12%)	0/403 (0.00%)
Pulmonary sepsis † 1	1/782 (0.13%)	0/806 (0.00%)	0/403 (0.00%)
Pyelonephritis † 1	0/782 (0.00%)	1/806 (0.12%)	0/403 (0.00%)
Respiratory tract infection † 1	1/782 (0.13%)	0/806 (0.00%)	0/403 (0.00%)
Sepsis † 1	13/782 (1.66%)	8/806 (0.99%)	3/403 (0.74%)
Septic shock † 1	1/782 (0.13%)	2/806 (0.25%)	2/403 (0.50%)
Sialoadenitis † 1	0/782 (0.00%)	0/806 (0.00%)	1/403 (0.25%)
Skin infection † 1	0/782 (0.00%)	0/806 (0.00%)	2/403 (0.50%)
Soft tissue infection † 1	1/782 (0.13%)	0/806 (0.00%)	0/403 (0.00%)
Staphylococcal infection † 1	1/782 (0.13%)	0/806 (0.00%)	0/403 (0.00%)
Stoma site infection † 1	0/782 (0.00%)	0/806 (0.00%)	1/403 (0.25%)
Streptococcal bacteraemia † 1	0/782 (0.00%)	0/806 (0.00%)	1/403 (0.25%)
Tonsillitis † 1	0/782 (0.00%)	0/806 (0.00%)	1/403 (0.25%)
Tuberculous pleurisy † 1	1/782 (0.13%)	0/806 (0.00%)	0/403 (0.00%)
Upper respiratory tract infection † 1	1/782 (0.13%)	0/806 (0.00%)	0/403 (0.00%)
Urinary tract infection † 1	3/782 (0.38%)	1/806 (0.12%)	6/403 (1.49%)
Urosepsis † 1	1/782 (0.13%)	0/806 (0.00%)	1/403 (0.25%)
Vascular device infection † 1	3/782 (0.38%)	1/806 (0.12%)	1/403 (0.25%)
Viral infection † 1	1/782 (0.13%)	0/806 (0.00%)	0/403 (0.00%)
Injury, poisoning and procedural complications
Anastomotic stenosis † 1	0/782 (0.00%)	0/806 (0.00%)	1/403 (0.25%)
Craniocerebral injury † 1	1/782 (0.13%)	0/806 (0.00%)	1/403 (0.25%)
Fall † 1	3/782 (0.38%)	1/806 (0.12%)	0/403 (0.00%)
Femoral neck fracture † 1	1/782 (0.13%)	0/806 (0.00%)	0/403 (0.00%)
Femur fracture † 1	1/782 (0.13%)	2/806 (0.25%)	0/403 (0.00%)
Fracture † 1	0/782 (0.00%)	1/806 (0.12%)	0/403 (0.00%)
Gastroenteritis radiation † 1	1/782 (0.13%)	0/806 (0.00%)	0/403 (0.00%)
Gastrointestinal stoma complication † 1	0/782 (0.00%)	1/806 (0.12%)	0/403 (0.00%)
Heart injury † 1	1/782 (0.13%)	0/806 (0.00%)	0/403 (0.00%)
Heat stroke † 1	1/782 (0.13%)	0/806 (0.00%)	0/403 (0.00%)
Hip fracture † 1	3/782 (0.38%)	0/806 (0.00%)	0/403 (0.00%)
Humerus fracture † 1	0/782 (0.00%)	1/806 (0.12%)	0/403 (0.00%)
Infusion related reaction † 1	6/782 (0.77%)	1/806 (0.12%)	0/403 (0.00%)
Lower limb fracture † 1	1/782 (0.13%)	0/806 (0.00%)	0/403 (0.00%)
Lumbar vertebral fracture † 1	0/782 (0.00%)	2/806 (0.25%)	0/403 (0.00%)
Overdose † 1	11/782 (1.41%)	6/806 (0.74%)	0/403 (0.00%)
Post procedural haematoma † 1	1/782 (0.13%)	0/806 (0.00%)	0/403 (0.00%)
Procedural complication † 1	1/782 (0.13%)	0/806 (0.00%)	0/403 (0.00%)
Radius fracture † 1	0/782 (0.00%)	0/806 (0.00%)	1/403 (0.25%)
Road traffic accident † 1	1/782 (0.13%)	0/806 (0.00%)	1/403 (0.25%)
Skin laceration † 1	0/782 (0.00%)	1/806 (0.12%)	0/403 (0.00%)
Soft tissue injury † 1	0/782 (0.00%)	1/806 (0.12%)	0/403 (0.00%)
Spinal compression fracture † 1	0/782 (0.00%)	0/806 (0.00%)	1/403 (0.25%)
Spinal fracture † 1	0/782 (0.00%)	1/806 (0.12%)	0/403 (0.00%)
Subdural haematoma † 1	0/782 (0.00%)	0/806 (0.00%)	1/403 (0.25%)
Synovial rupture † 1	0/782 (0.00%)	0/806 (0.00%)	1/403 (0.25%)
Thoracic vertebral fracture † 1	0/782 (0.00%)	2/806 (0.25%)	0/403 (0.00%)
Vascular injury † 1	0/782 (0.00%)	1/806 (0.12%)	0/403 (0.00%)
Investigations
Alanine aminotransferase increased † 1	1/782 (0.13%)	0/806 (0.00%)	2/403 (0.50%)
Amylase increased † 1	0/782 (0.00%)	0/806 (0.00%)	1/403 (0.25%)
Aspartate aminotransferase increased † 1	2/782 (0.26%)	0/806 (0.00%)	0/403 (0.00%)
Blood alkaline phosphatase increased † 1	1/782 (0.13%)	0/806 (0.00%)	0/403 (0.00%)
Blood bilirubin increased † 1	6/782 (0.77%)	1/806 (0.12%)	2/403 (0.50%)
Blood corticotrophin decreased † 1	0/782 (0.00%)	0/806 (0.00%)	1/403 (0.25%)
Blood creatinine increased † 1	0/782 (0.00%)	1/806 (0.12%)	2/403 (0.50%)
Electrocardiogram ST segment elevation † 1	1/782 (0.13%)	0/806 (0.00%)	0/403 (0.00%)
General physical condition abnormal † 1	2/782 (0.26%)	1/806 (0.12%)	1/403 (0.25%)
Haemoglobin decreased † 1	0/782 (0.00%)	0/806 (0.00%)	1/403 (0.25%)
Hepatitis C virus test positive † 1	1/782 (0.13%)	0/806 (0.00%)	0/403 (0.00%)
Lipase increased † 1	1/782 (0.13%)	0/806 (0.00%)	0/403 (0.00%)
Liver function test increased † 1	0/782 (0.00%)	0/806 (0.00%)	2/403 (0.50%)
Neutrophil count decreased † 1	3/782 (0.38%)	3/806 (0.37%)	0/403 (0.00%)
Platelet count decreased † 1	3/782 (0.38%)	4/806 (0.50%)	1/403 (0.25%)
Transaminases increased † 1	0/782 (0.00%)	0/806 (0.00%)	2/403 (0.50%)
Troponin increased † 1	0/782 (0.00%)	1/806 (0.12%)	0/403 (0.00%)
Weight decreased † 1	0/782 (0.00%)	0/806 (0.00%)	1/403 (0.25%)
Metabolism and nutrition disorders
Decreased appetite † 1	7/782 (0.90%)	9/806 (1.12%)	6/403 (1.49%)
Dehydration † 1	8/782 (1.02%)	7/806 (0.87%)	3/403 (0.74%)
Diabetes mellitus † 1	1/782 (0.13%)	1/806 (0.12%)	0/403 (0.00%)
Diabetes mellitus inadequate control † 1	1/782 (0.13%)	0/806 (0.00%)	0/403 (0.00%)
Diabetic ketoacidosis † 1	0/782 (0.00%)	0/806 (0.00%)	1/403 (0.25%)
Diabetic metabolic decompensation † 1	0/782 (0.00%)	1/806 (0.12%)	0/403 (0.00%)
Electrolyte imbalance † 1	2/782 (0.26%)	1/806 (0.12%)	1/403 (0.25%)
Failure to thrive † 1	0/782 (0.00%)	1/806 (0.12%)	0/403 (0.00%)
Gout † 1	1/782 (0.13%)	0/806 (0.00%)	0/403 (0.00%)
Hypercalcaemia † 1	0/782 (0.00%)	2/806 (0.25%)	0/403 (0.00%)
Hyperglycaemia † 1	0/782 (0.00%)	2/806 (0.25%)	1/403 (0.25%)
Hyperkalaemia † 1	0/782 (0.00%)	0/806 (0.00%)	2/403 (0.50%)
Hypernatraemia † 1	1/782 (0.13%)	0/806 (0.00%)	0/403 (0.00%)
Hypoalbuminaemia † 1	1/782 (0.13%)	0/806 (0.00%)	3/403 (0.74%)
Hypoglycaemia † 1	1/782 (0.13%)	1/806 (0.12%)	2/403 (0.50%)
Hypokalaemia † 1	3/782 (0.38%)	5/806 (0.62%)	2/403 (0.50%)
Hyponatraemia † 1	4/782 (0.51%)	1/806 (0.12%)	3/403 (0.74%)
Hypophagia † 1	0/782 (0.00%)	1/806 (0.12%)	0/403 (0.00%)
Hypoproteinaemia † 1	0/782 (0.00%)	0/806 (0.00%)	1/403 (0.25%)
Malnutrition † 1	0/782 (0.00%)	2/806 (0.25%)	1/403 (0.25%)
Metabolic acidosis † 1	0/782 (0.00%)	0/806 (0.00%)	1/403 (0.25%)
Type 1 diabetes mellitus † 1	0/782 (0.00%)	0/806 (0.00%)	1/403 (0.25%)
Type 2 diabetes mellitus † 1	1/782 (0.13%)	0/806 (0.00%)	1/403 (0.25%)
Musculoskeletal and connective tissue disorders
Arthralgia † 1	0/782 (0.00%)	0/806 (0.00%)	1/403 (0.25%)
Arthritis † 1	1/782 (0.13%)	0/806 (0.00%)	0/403 (0.00%)
Back pain † 1	4/782 (0.51%)	4/806 (0.50%)	1/403 (0.25%)
Bone lesion † 1	1/782 (0.13%)	0/806 (0.00%)	0/403 (0.00%)
Bone pain † 1	2/782 (0.26%)	0/806 (0.00%)	0/403 (0.00%)
Fistula † 1	1/782 (0.13%)	0/806 (0.00%)	0/403 (0.00%)
Intervertebral disc protrusion † 1	0/782 (0.00%)	0/806 (0.00%)	1/403 (0.25%)
Mixed connective tissue disease † 1	1/782 (0.13%)	0/806 (0.00%)	0/403 (0.00%)
Muscular weakness † 1	1/782 (0.13%)	0/806 (0.00%)	0/403 (0.00%)
Musculoskeletal chest pain † 1	0/782 (0.00%)	1/806 (0.12%)	0/403 (0.00%)
Myositis † 1	0/782 (0.00%)	2/806 (0.25%)	3/403 (0.74%)
Osteolysis † 1	1/782 (0.13%)	0/806 (0.00%)	0/403 (0.00%)
Pain in extremity † 1	0/782 (0.00%)	0/806 (0.00%)	1/403 (0.25%)
Pathological fracture † 1	0/782 (0.00%)	0/806 (0.00%)	1/403 (0.25%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma † 1	1/782 (0.13%)	0/806 (0.00%)	0/403 (0.00%)
Cancer pain † 1	1/782 (0.13%)	0/806 (0.00%)	0/403 (0.00%)
Gastric cancer † 1	1/782 (0.13%)	1/806 (0.12%)	1/403 (0.25%)
Gastric neoplasm † 1	2/782 (0.26%)	1/806 (0.12%)	0/403 (0.00%)
Laryngeal squamous cell carcinoma † 1	0/782 (0.00%)	1/806 (0.12%)	0/403 (0.00%)
Malignant ascites † 1	1/782 (0.13%)	1/806 (0.12%)	0/403 (0.00%)
Malignant neoplasm progression † 1	246/782 (31.46%)	242/806 (30.02%)	112/403 (27.79%)
Malignant pleural effusion † 1	1/782 (0.13%)	0/806 (0.00%)	0/403 (0.00%)
Metastases to bone † 1	1/782 (0.13%)	0/806 (0.00%)	0/403 (0.00%)
Metastases to central nervous system † 1	4/782 (0.51%)	4/806 (0.50%)	0/403 (0.00%)
Metastases to liver † 1	0/782 (0.00%)	1/806 (0.12%)	0/403 (0.00%)
Metastases to meninges † 1	1/782 (0.13%)	1/806 (0.12%)	0/403 (0.00%)
Metastasis † 1	0/782 (0.00%)	1/806 (0.12%)	0/403 (0.00%)
Metastatic gastric cancer † 1	0/782 (0.00%)	2/806 (0.25%)	0/403 (0.00%)
Myelodysplastic syndrome † 1	1/782 (0.13%)	0/806 (0.00%)	0/403 (0.00%)
Neoplasm malignant † 1	1/782 (0.13%)	1/806 (0.12%)	0/403 (0.00%)
Neoplasm progression † 1	2/782 (0.26%)	0/806 (0.00%)	0/403 (0.00%)
Oesophageal adenocarcinoma † 1	0/782 (0.00%)	1/806 (0.12%)	0/403 (0.00%)
Oesophageal cancer metastatic † 1	1/782 (0.13%)	0/806 (0.00%)	0/403 (0.00%)
Rectal cancer † 1	0/782 (0.00%)	1/806 (0.12%)	0/403 (0.00%)
Second primary malignancy † 1	1/782 (0.13%)	0/806 (0.00%)	0/403 (0.00%)
Squamous cell carcinoma † 1	1/782 (0.13%)	0/806 (0.00%)	0/403 (0.00%)
Squamous cell carcinoma of lung † 1	1/782 (0.13%)	0/806 (0.00%)	0/403 (0.00%)
Tumour associated fever † 1	1/782 (0.13%)	0/806 (0.00%)	0/403 (0.00%)
Tumour haemorrhage † 1	3/782 (0.38%)	0/806 (0.00%)	2/403 (0.50%)
Tumour necrosis † 1	1/782 (0.13%)	0/806 (0.00%)	0/403 (0.00%)
Tumour obstruction † 1	0/782 (0.00%)	1/806 (0.12%)	0/403 (0.00%)
Tumour pain † 1	2/782 (0.26%)	1/806 (0.12%)	2/403 (0.50%)
Tumour ulceration † 1	1/782 (0.13%)	0/806 (0.00%)	0/403 (0.00%)
Nervous system disorders
Aphasia † 1	0/782 (0.00%)	2/806 (0.25%)	0/403 (0.00%)
Brain oedema † 1	1/782 (0.13%)	0/806 (0.00%)	0/403 (0.00%)
Brain stem infarction † 1	1/782 (0.13%)	0/806 (0.00%)	0/403 (0.00%)
Central nervous system lesion † 1	0/782 (0.00%)	1/806 (0.12%)	0/403 (0.00%)
Cerebellar syndrome † 1	0/782 (0.00%)	1/806 (0.12%)	0/403 (0.00%)
Cerebral artery embolism † 1	0/782 (0.00%)	0/806 (0.00%)	1/403 (0.25%)
Cerebral infarction † 1	2/782 (0.26%)	0/806 (0.00%)	1/403 (0.25%)
Cerebral ischaemia † 1	2/782 (0.26%)	1/806 (0.12%)	0/403 (0.00%)
Cerebrovascular accident † 1	3/782 (0.38%)	1/806 (0.12%)	1/403 (0.25%)
Depressed level of consciousness † 1	0/782 (0.00%)	0/806 (0.00%)	1/403 (0.25%)
Diabetic hyperosmolar coma † 1	0/782 (0.00%)	0/806 (0.00%)	1/403 (0.25%)
Dizziness † 1	0/782 (0.00%)	1/806 (0.12%)	1/403 (0.25%)
Encephalitis autoimmune † 1	0/782 (0.00%)	0/806 (0.00%)	1/403 (0.25%)
Encephalopathy † 1	1/782 (0.13%)	0/806 (0.00%)	0/403 (0.00%)
Epilepsy † 1	1/782 (0.13%)	0/806 (0.00%)	0/403 (0.00%)
Facial paresis † 1	0/782 (0.00%)	0/806 (0.00%)	2/403 (0.50%)
Guillain-Barre syndrome † 1	1/782 (0.13%)	0/806 (0.00%)	0/403 (0.00%)
Headache † 1	2/782 (0.26%)	2/806 (0.25%)	0/403 (0.00%)
Hemiparesis † 1	0/782 (0.00%)	0/806 (0.00%)	1/403 (0.25%)
Hypokinesia † 1	0/782 (0.00%)	1/806 (0.12%)	0/403 (0.00%)
Immune-mediated neuropathy † 1	0/782 (0.00%)	0/806 (0.00%)	1/403 (0.25%)
Intracranial pressure increased † 1	0/782 (0.00%)	1/806 (0.12%)	0/403 (0.00%)
Ischaemic stroke † 1	2/782 (0.26%)	2/806 (0.25%)	0/403 (0.00%)
Metabolic encephalopathy † 1	0/782 (0.00%)	1/806 (0.12%)	0/403 (0.00%)
Neuritis † 1	0/782 (0.00%)	0/806 (0.00%)	1/403 (0.25%)
Neuropathy peripheral † 1	1/782 (0.13%)	1/806 (0.12%)	1/403 (0.25%)
Polyneuropathy † 1	0/782 (0.00%)	0/806 (0.00%)	1/403 (0.25%)
Presyncope † 1	1/782 (0.13%)	0/806 (0.00%)	1/403 (0.25%)
Seizure † 1	1/782 (0.13%)	1/806 (0.12%)	1/403 (0.25%)
Spinal cord compression † 1	2/782 (0.26%)	0/806 (0.00%)	1/403 (0.25%)
Subarachnoid haemorrhage † 1	0/782 (0.00%)	0/806 (0.00%)	1/403 (0.25%)
Syncope † 1	9/782 (1.15%)	4/806 (0.50%)	2/403 (0.50%)
Transient ischaemic attack † 1	2/782 (0.26%)	2/806 (0.25%)	0/403 (0.00%)
Product Issues
Device breakage † 1	0/782 (0.00%)	1/806 (0.12%)	0/403 (0.00%)
Device dislocation † 1	3/782 (0.38%)	2/806 (0.25%)	2/403 (0.50%)
Device leakage † 1	0/782 (0.00%)	1/806 (0.12%)	0/403 (0.00%)
Device malfunction † 1	0/782 (0.00%)	0/806 (0.00%)	1/403 (0.25%)
Device occlusion † 1	3/782 (0.38%)	0/806 (0.00%)	0/403 (0.00%)
Stent malfunction † 1	0/782 (0.00%)	1/806 (0.12%)	0/403 (0.00%)
Psychiatric disorders
Bipolar disorder † 1	0/782 (0.00%)	1/806 (0.12%)	0/403 (0.00%)
Depression † 1	1/782 (0.13%)	0/806 (0.00%)	0/403 (0.00%)
Eating disorder † 1	0/782 (0.00%)	0/806 (0.00%)	1/403 (0.25%)
Mental status changes † 1	0/782 (0.00%)	2/806 (0.25%)	0/403 (0.00%)
Suicide attempt † 1	1/782 (0.13%)	2/806 (0.25%)	0/403 (0.00%)
Renal and urinary disorders
Acute kidney injury † 1	6/782 (0.77%)	3/806 (0.37%)	9/403 (2.23%)
Cystitis noninfective † 1	1/782 (0.13%)	0/806 (0.00%)	0/403 (0.00%)
Dysuria † 1	0/782 (0.00%)	1/806 (0.12%)	1/403 (0.25%)
Haematuria † 1	1/782 (0.13%)	0/806 (0.00%)	0/403 (0.00%)
Hydronephrosis † 1	0/782 (0.00%)	2/806 (0.25%)	1/403 (0.25%)
Nephritis † 1	1/782 (0.13%)	0/806 (0.00%)	1/403 (0.25%)
Nephrolithiasis † 1	0/782 (0.00%)	2/806 (0.25%)	0/403 (0.00%)
Prerenal failure † 1	1/782 (0.13%)	0/806 (0.00%)	0/403 (0.00%)
Renal failure † 1	1/782 (0.13%)	3/806 (0.37%)	0/403 (0.00%)
Renal impairment † 1	1/782 (0.13%)	0/806 (0.00%)	0/403 (0.00%)
Tubulointerstitial nephritis † 1	1/782 (0.13%)	0/806 (0.00%)	0/403 (0.00%)
Ureteric dilatation † 1	0/782 (0.00%)	1/806 (0.12%)	0/403 (0.00%)
Ureterolithiasis † 1	0/782 (0.00%)	1/806 (0.12%)	0/403 (0.00%)
Urinary retention † 1	0/782 (0.00%)	1/806 (0.12%)	2/403 (0.50%)
Urinary tract obstruction † 1	1/782 (0.13%)	0/806 (0.00%)	1/403 (0.25%)
Reproductive system and breast disorders
Benign prostatic hyperplasia † 1	0/782 (0.00%)	1/806 (0.12%)	0/403 (0.00%)
Vaginal haemorrhage † 1	1/782 (0.13%)	1/806 (0.12%)	0/403 (0.00%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure † 1	0/782 (0.00%)	2/806 (0.25%)	0/403 (0.00%)
Asphyxia † 1	0/782 (0.00%)	0/806 (0.00%)	1/403 (0.25%)
Bronchospasm † 1	0/782 (0.00%)	0/806 (0.00%)	1/403 (0.25%)
Chronic obstructive pulmonary disease † 1	0/782 (0.00%)	1/806 (0.12%)	1/403 (0.25%)
Cough † 1	1/782 (0.13%)	0/806 (0.00%)	0/403 (0.00%)
Dyspnoea † 1	0/782 (0.00%)	2/806 (0.25%)	3/403 (0.74%)
Haemothorax † 1	1/782 (0.13%)	0/806 (0.00%)	0/403 (0.00%)
Hiccups † 1	0/782 (0.00%)	1/806 (0.12%)	0/403 (0.00%)
Hypoxia † 1	2/782 (0.26%)	0/806 (0.00%)	0/403 (0.00%)
Immune-mediated lung disease † 1	0/782 (0.00%)	0/806 (0.00%)	1/403 (0.25%)
Interstitial lung disease † 1	3/782 (0.38%)	2/806 (0.25%)	2/403 (0.50%)
Laryngeal haemorrhage † 1	1/782 (0.13%)	0/806 (0.00%)	0/403 (0.00%)
Mediastinal effusion † 1	0/782 (0.00%)	1/806 (0.12%)	0/403 (0.00%)
Oropharyngeal discomfort † 1	0/782 (0.00%)	1/806 (0.12%)	0/403 (0.00%)
Pleural effusion † 1	5/782 (0.64%)	6/806 (0.74%)	6/403 (1.49%)
Pneumonia aspiration † 1	5/782 (0.64%)	0/806 (0.00%)	1/403 (0.25%)
Pneumonitis † 1	19/782 (2.43%)	1/806 (0.12%)	7/403 (1.74%)
Pneumothorax † 1	3/782 (0.38%)	0/806 (0.00%)	0/403 (0.00%)
Pulmonary artery thrombosis † 1	1/782 (0.13%)	1/806 (0.12%)	0/403 (0.00%)
Pulmonary embolism † 1	14/782 (1.79%)	18/806 (2.23%)	9/403 (2.23%)
Pulmonary hypertension † 1	1/782 (0.13%)	0/806 (0.00%)	0/403 (0.00%)
Pulmonary oedema † 1	1/782 (0.13%)	0/806 (0.00%)	0/403 (0.00%)
Respiratory failure † 1	5/782 (0.64%)	3/806 (0.37%)	2/403 (0.50%)
Restrictive pulmonary disease † 1	1/782 (0.13%)	0/806 (0.00%)	0/403 (0.00%)
Skin and subcutaneous tissue disorders
Diabetic foot † 1	1/782 (0.13%)	1/806 (0.12%)	0/403 (0.00%)
Drug eruption † 1	2/782 (0.26%)	0/806 (0.00%)	0/403 (0.00%)
Eczema asteatotic † 1	0/782 (0.00%)	0/806 (0.00%)	1/403 (0.25%)
Ischaemic skin ulcer † 1	1/782 (0.13%)	0/806 (0.00%)	0/403 (0.00%)
Rash † 1	0/782 (0.00%)	0/806 (0.00%)	3/403 (0.74%)
Rash erythematous † 1	0/782 (0.00%)	0/806 (0.00%)	1/403 (0.25%)
Rash maculo-papular † 1	2/782 (0.26%)	0/806 (0.00%)	2/403 (0.50%)
Skin lesion † 1	0/782 (0.00%)	1/806 (0.12%)	0/403 (0.00%)
Toxic epidermal necrolysis † 1	0/782 (0.00%)	0/806 (0.00%)	1/403 (0.25%)
Urticaria † 1	0/782 (0.00%)	1/806 (0.12%)	0/403 (0.00%)
Surgical and medical procedures
Gastrectomy † 1	1/782 (0.13%)	0/806 (0.00%)	0/403 (0.00%)
Tumour excision † 1	0/782 (0.00%)	1/806 (0.12%)	0/403 (0.00%)
Vascular disorders
Axillary vein thrombosis † 1	0/782 (0.00%)	0/806 (0.00%)	1/403 (0.25%)
Capillary leak syndrome † 1	0/782 (0.00%)	0/806 (0.00%)	1/403 (0.25%)
Circulatory collapse † 1	0/782 (0.00%)	1/806 (0.12%)	0/403 (0.00%)
Deep vein thrombosis † 1	3/782 (0.38%)	3/806 (0.37%)	3/403 (0.74%)
Embolism † 1	6/782 (0.77%)	1/806 (0.12%)	0/403 (0.00%)
Hypotension † 1	2/782 (0.26%)	2/806 (0.25%)	0/403 (0.00%)
Hypovolaemic shock † 1	1/782 (0.13%)	0/806 (0.00%)	0/403 (0.00%)
Jugular vein thrombosis † 1	1/782 (0.13%)	1/806 (0.12%)	0/403 (0.00%)
Obstructive shock † 1	0/782 (0.00%)	1/806 (0.12%)	0/403 (0.00%)
Peripheral artery occlusion † 1	0/782 (0.00%)	1/806 (0.12%)	0/403 (0.00%)
Peripheral ischaemia † 1	1/782 (0.13%)	0/806 (0.00%)	0/403 (0.00%)
Peripheral venous disease † 1	0/782 (0.00%)	1/806 (0.12%)	0/403 (0.00%)
Shock † 1	1/782 (0.13%)	0/806 (0.00%)	0/403 (0.00%)
Shock haemorrhagic † 1	0/782 (0.00%)	1/806 (0.12%)	0/403 (0.00%)
Subclavian artery stenosis † 1	1/782 (0.13%)	0/806 (0.00%)	0/403 (0.00%)
Thrombosis † 1	0/782 (0.00%)	1/806 (0.12%)	0/403 (0.00%)
Venous thrombosis † 1	1/782 (0.13%)	1/806 (0.12%)	0/403 (0.00%)
1 Term from vocabulary, 24.0; † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Arm A: Nivolumab + Chemotherapy (XELOX or FOLFOX)	Arm B: Chemotherapy (XELOX or FOLFOX)	Arm C: Nivolumab + Ipilimumab
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	763/782 (97.57%)	756/806 (93.80%)	369/403 (91.56%)
Blood and lymphatic system disorders
Anaemia † 1	312/782 (39.90%)	276/806 (34.24%)	132/403 (32.75%)
Leukopenia † 1	75/782 (9.59%)	64/806 (7.94%)	9/403 (2.23%)
Neutropenia † 1	218/782 (27.88%)	203/806 (25.19%)	18/403 (4.47%)
Thrombocytopenia † 1	173/782 (22.12%)	160/806 (19.85%)	10/403 (2.48%)
Endocrine disorders
Hyperthyroidism † 1	30/782 (3.84%)	2/806 (0.25%)	26/403 (6.45%)
Hypothyroidism † 1	82/782 (10.49%)	13/806 (1.61%)	54/403 (13.40%)
Gastrointestinal disorders
Abdominal distension † 1	56/782 (7.16%)	43/806 (5.33%)	26/403 (6.45%)
Abdominal pain † 1	159/782 (20.33%)	134/806 (16.63%)	66/403 (16.38%)
Abdominal pain upper † 1	73/782 (9.34%)	75/806 (9.31%)	36/403 (8.93%)
Constipation † 1	201/782 (25.70%)	177/806 (21.96%)	77/403 (19.11%)
Diarrhoea † 1	309/782 (39.51%)	286/806 (35.48%)	111/403 (27.54%)
Dysphagia † 1	64/782 (8.18%)	64/806 (7.94%)	32/403 (7.94%)
Nausea † 1	385/782 (49.23%)	362/806 (44.91%)	101/403 (25.06%)
Stomatitis † 1	67/782 (8.57%)	57/806 (7.07%)	13/403 (3.23%)
Vomiting † 1	247/782 (31.59%)	233/806 (28.91%)	72/403 (17.87%)
General disorders
Asthenia † 1	119/782 (15.22%)	127/806 (15.76%)	47/403 (11.66%)
Fatigue † 1	271/782 (34.65%)	234/806 (29.03%)	103/403 (25.56%)
Malaise † 1	40/782 (5.12%)	41/806 (5.09%)	19/403 (4.71%)
Mucosal inflammation † 1	78/782 (9.97%)	47/806 (5.83%)	7/403 (1.74%)
Oedema peripheral † 1	93/782 (11.89%)	66/806 (8.19%)	44/403 (10.92%)
Pyrexia † 1	143/782 (18.29%)	93/806 (11.54%)	93/403 (23.08%)
Immune system disorders
Hypersensitivity † 1	51/782 (6.52%)	12/806 (1.49%)	6/403 (1.49%)
Injury, poisoning and procedural complications
Infusion related reaction † 1	67/782 (8.57%)	31/806 (3.85%)	12/403 (2.98%)
Investigations
Alanine aminotransferase increased † 1	118/782 (15.09%)	86/806 (10.67%)	76/403 (18.86%)
Amylase increased † 1	91/782 (11.64%)	45/806 (5.58%)	48/403 (11.91%)
Aspartate aminotransferase increased † 1	163/782 (20.84%)	113/806 (14.02%)	81/403 (20.10%)
Blood alkaline phosphatase increased † 1	107/782 (13.68%)	66/806 (8.19%)	47/403 (11.66%)
Blood bilirubin increased † 1	83/782 (10.61%)	61/806 (7.57%)	30/403 (7.44%)
Blood creatinine increased † 1	42/782 (5.37%)	22/806 (2.73%)	35/403 (8.68%)
Lipase increased † 1	108/782 (13.81%)	72/806 (8.93%)	52/403 (12.90%)
Neutrophil count decreased † 1	171/782 (21.87%)	139/806 (17.25%)	19/403 (4.71%)
Platelet count decreased † 1	172/782 (21.99%)	132/806 (16.38%)	21/403 (5.21%)
Weight decreased † 1	139/782 (17.77%)	128/806 (15.88%)	60/403 (14.89%)
White blood cell count decreased † 1	123/782 (15.73%)	92/806 (11.41%)	16/403 (3.97%)
Metabolism and nutrition disorders
Decreased appetite † 1	236/782 (30.18%)	226/806 (28.04%)	111/403 (27.54%)
Hyperglycaemia † 1	84/782 (10.74%)	63/806 (7.82%)	37/403 (9.18%)
Hypoalbuminaemia † 1	109/782 (13.94%)	72/806 (8.93%)	62/403 (15.38%)
Hypocalcaemia † 1	53/782 (6.78%)	37/806 (4.59%)	21/403 (5.21%)
Hypokalaemia † 1	93/782 (11.89%)	74/806 (9.18%)	37/403 (9.18%)
Hyponatraemia † 1	72/782 (9.21%)	51/806 (6.33%)	53/403 (13.15%)
Musculoskeletal and connective tissue disorders
Arthralgia † 1	75/782 (9.59%)	42/806 (5.21%)	29/403 (7.20%)
Back pain † 1	86/782 (11.00%)	66/806 (8.19%)	39/403 (9.68%)
Pain in extremity † 1	43/782 (5.50%)	20/806 (2.48%)	9/403 (2.23%)
Nervous system disorders
Dizziness † 1	56/782 (7.16%)	58/806 (7.20%)	16/403 (3.97%)
Dysgeusia † 1	48/782 (6.14%)	43/806 (5.33%)	10/403 (2.48%)
Headache † 1	89/782 (11.38%)	52/806 (6.45%)	33/403 (8.19%)
Hypoaesthesia † 1	45/782 (5.75%)	42/806 (5.21%)	6/403 (1.49%)
Neuropathy peripheral † 1	238/782 (30.43%)	210/806 (26.05%)	7/403 (1.74%)
Paraesthesia † 1	72/782 (9.21%)	78/806 (9.68%)	7/403 (1.74%)
Peripheral sensory neuropathy † 1	146/782 (18.67%)	128/806 (15.88%)	13/403 (3.23%)
Psychiatric disorders
Insomnia † 1	61/782 (7.80%)	69/806 (8.56%)	36/403 (8.93%)
Respiratory, thoracic and mediastinal disorders
Cough † 1	100/782 (12.79%)	63/806 (7.82%)	51/403 (12.66%)
Dyspnoea † 1	66/782 (8.44%)	49/806 (6.08%)	37/403 (9.18%)
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysaesthesia syndrome † 1	108/782 (13.81%)	96/806 (11.91%)	0/403 (0.00%)
Pruritus † 1	79/782 (10.10%)	18/806 (2.23%)	72/403 (17.87%)
Rash † 1	91/782 (11.64%)	23/806 (2.85%)	77/403 (19.11%)
Rash maculo-papular † 1	28/782 (3.58%)	7/806 (0.87%)	41/403 (10.17%)
Vascular disorders
Hypertension † 1	48/782 (6.14%)	41/806 (5.09%)	17/403 (4.22%)
Hypotension † 1	26/782 (3.32%)	21/806 (2.61%)	21/403 (5.21%)
1 Term from vocabulary, 24.0; † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

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

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.

Results Point of Contact

• Name/Title: Bristol-Myers Squibb Study Director
• Organization: Bristol-Myers Squibb
• Phone: Please Email
• EMail: Clinical.Trials@bms.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Janjigian YY, Shitara K, Moehler M, Garrido M, Salman P, Shen L, Wyrwicz L, Yamaguchi K, Skoczylas T, Campos Bragagnoli A, Liu T, Schenker M, Yanez P, Tehfe M, Kowalyszyn R, Karamouzis MV, Bruges R, Zander T, Pazo-Cid R, Hitre E, Feeney K, Cleary JM, Poulart V, Cullen D, Lei M, Xiao H, Kondo K, Li M, Ajani JA. First-line nivolumab plus chemotherapy versus chemotherapy alone for advanced gastric, gastro-oesophageal junction, and oesophageal adenocarcinoma (CheckMate 649): a randomised, open-label, phase 3 trial. Lancet. 2021 Jul 3;398(10294):27-40. doi: 10.1016/S0140-6736(21)00797-2. Epub 2021 Jun 5.

• Responsible Party: Bristol-Myers Squibb
• ClinicalTrials.gov Identifier: NCT02872116
• Other Study ID Numbers: CA209-649; 2016-001018-76 ( EudraCT Number )
• First Submitted: August 16, 2016
• First Posted: August 19, 2016
• Results First Submitted: May 18, 2022
• Results First Posted: June 28, 2022
• Last Update Posted: December 4, 2023