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Clinical Trial Results:
A Randomized, Open-label, Phase II Clinical Trial of Relatlimab (anti-LAG-3) and Nivolumab in Combination with Chemotherapy Versus Nivolumab in Combination with Chemotherapy as First- Line Treatment in Patients with Gastric or Gastroesophageal Junction Adenocarcinoma

Summary
EudraCT number	2018-001069-18
Trial protocol	CZ DE GB ES NO BE PL AT IT
Global end of trial date	18 Jan 2024

Results information
Results version number	v1(current)
This version publication date	31 Jan 2025
First version publication date	31 Jan 2025
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

CA224-060

ISRCTN number

US NCT number

WHO universal trial number (UTN)

Sponsor organisation name

Bristol-Myers Squibb

Sponsor organisation address

Chaussée de la Hulpe 185, Brussels, Belgium, 1170

Public contact

EU Study Start-Up Unit, Bristol-Myers Squibb International Corporation, Clinical.Trials@bms.com

Scientific contact

Bristol-Myers Squibb Study Director, Bristol-Myers Squibb, Clinical.Trials@bms.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

28 Feb 2024

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

18 Jan 2024

Was the trial ended prematurely?

Main objective of the trial

To assess the efficacy of treatment with BMS-986213 (fixed-dose combination [FDC] relatlimab/nivolumab) plus investigator’s choice chemotherapy compared with nivolumab in combination with investigator’s choice chemotherapy in participants with previously untreated, unresectable, and either locally advanced or metastatic gastric cancer (GC) or GEJ adenocarcinoma in the LAG-3 positive population.

Protection of trial subjects

The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Conference on Harmonization Good Clinical Practice Guidelines. All the local regulatory requirements pertinent to safety of trial subjects were followed.

Background therapy

Evidence for comparator

Actual start date of recruitment

16 Oct 2018

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Austria: 2

Country: Number of subjects enrolled

Belgium: 10

Country: Number of subjects enrolled

Czechia: 12

Country: Number of subjects enrolled

France: 13

Country: Number of subjects enrolled

Germany: 39

Country: Number of subjects enrolled

Italy: 5

Country: Number of subjects enrolled

Norway: 11

Country: Number of subjects enrolled

Poland: 4

Country: Number of subjects enrolled

Spain: 25

Country: Number of subjects enrolled

United Kingdom: 27

Country: Number of subjects enrolled

Canada: 14

Country: Number of subjects enrolled

United States: 30

Country: Number of subjects enrolled

Argentina: 20

Country: Number of subjects enrolled

Australia: 46

Country: Number of subjects enrolled

Chile: 9

Country: Number of subjects enrolled

Puerto Rico: 2

Country: Number of subjects enrolled

Singapore: 5

Worldwide total number of subjects

274

EEA total number of subjects

121

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

161

From 65 to 84 years

113

85 years and over

Subject disposition

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Recruitment details

Screening details

274 participants randomized and 271 treated.

Period 1 title

Pre-treatment

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

BMS986213 + Chemotherapy

Arm description

BMS986213 Q3W + Investigator Choice (IC) Chemotherapy

Arm type

Experimental

Investigational medicinal product name

BMS986213

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intravenous use

Dosage and administration details

Relatlimab 120 mg every 3 weeks

Investigational medicinal product name

Xelox

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Oxaliplatin 130mg/m^2 Day 1 of each cycle

Investigational medicinal product name

Xelox

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Capecitabine 1000mg/m^2 twice daily Day 1 - Day 14 of each cycle

Investigational medicinal product name

BMS986213

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intravenous use

Dosage and administration details

Nivolumab 360 mg every 3 weeks

Investigational medicinal product name

Folfox

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Oxaliplatin 85mg/m^2 Day 1

Investigational medicinal product name

Folfox

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intravenous use

Dosage and administration details

Leucovorin 400 mg/m^2 Day 1

Investigational medicinal product name

Folfox

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intravenous use

Dosage and administration details

fluorouracil 400 mg/m^2 Day 1

Investigational medicinal product name

Folfox

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intravenous use

Dosage and administration details

fluorouracil 400 mg/m^2 continuous infusion for over 24 hours daily Day 1 and 2 of each cycle, every 2 weeks.

Investigational medicinal product name

Sox

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Oxaliplatin 130mg/m^2 twice daily Day 1 to 14 of each cycle, every 3 weeks

Investigational medicinal product name

Sox

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Oxaliplatin 130 mg/m^2 Day 1

Nivolumab + Chemotherapy

Arm description

Nivolumab Q3W + Investigator Choice (IC) Chemotherapy

Arm type

Active comparator

Investigational medicinal product name

Nivolumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intravenous use

Dosage and administration details

360 mg every 3 weeks

Investigational medicinal product name

Xelox

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Capecitabine 1000mg/m^2 twice daily Day 1 - Day 14 of each cycle

Investigational medicinal product name

Xelox

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Oxaliplatin 130mg/m^2 Day 1 of each cycle

Investigational medicinal product name

Nivolumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intravenous use

Dosage and administration details

480 mg every 4 weeks

Investigational medicinal product name

Sox

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Oxaliplatin 130mg/m^2 twice daily Day 1 to 14 of each cycle, every 3 weeks

Investigational medicinal product name

Folfox

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intravenous use

Dosage and administration details

fluorouracil 400 mg/m^2 continuous infusion for over 24 hours daily Day 1 and 2 of each cycle, every 2 weeks.

Investigational medicinal product name

Folfox

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intravenous use

Dosage and administration details

fluorouracil 400 mg/m^2 Day 1

Investigational medicinal product name

Folfox

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intravenous use

Dosage and administration details

Leucovorin 400 mg/m^2 Day 1

Investigational medicinal product name

Sox

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Oxaliplatin 130 mg/m^2 Day 1

Investigational medicinal product name

Folfox

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Oxaliplatin 85mg/m^2 Day 1

Number of subjects in period 1	BMS986213 + Chemotherapy	Nivolumab + Chemotherapy
Started	138	136
Completed	136	135
Not completed	2	1
Other reasons	1	-
Participant no longer met study criteria	1	1

Period 2 title

Treatment

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

BMS986213 + Chemotherapy

Arm description

BMS986213 Q3W + Investigator Choice (IC) Chemotherapy XELOX Q3W or BMS986213 Q4W + IC Chemotherapy FOLFOX Q2W or BMS986213 Q3W + IC Chemotherapy SOX Q3W

Arm type

Experimental

Investigational medicinal product name

BMS986213

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intravenous use

Dosage and administration details

Relatlimab 120 mg every 3 weeks

Investigational medicinal product name

BMS986213

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intravenous use

Dosage and administration details

Nivolumab 360 mg every 3 weeks

Investigational medicinal product name

Xelox

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Oxaliplatin 130mg/m^2 Day 1 of each cycle

Investigational medicinal product name

Xelox

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Capecitabine 1000mg/m^2 twice daily Day 1 - Day 14 of each cycle

Investigational medicinal product name

Folfox

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Oxaliplatin 85mg/m^2 Day 1

Investigational medicinal product name

Folfox

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intravenous use

Dosage and administration details

fluorouracil 400 mg/m^2 Day 1

Investigational medicinal product name

Folfox

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intravenous use

Dosage and administration details

Leucovorin 400 mg/m^2 Day 1

Investigational medicinal product name

Sox

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Oxaliplatin 130mg/m^2 twice daily Day 1 to 14 of each cycle, every 3 weeks

Investigational medicinal product name

Folfox

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intravenous use

Dosage and administration details

fluorouracil 400 mg/m^2 continuous infusion for over 24 hours daily Day 1 and 2 of each cycle, every 2 weeks.

Investigational medicinal product name

Sox

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Oxaliplatin 130 mg/m^2 Day 1

Nivolumab + Chemotherapy

Arm description

Nivolumab 360 mg Q3W + Investigator Choice (IC) Chemotherapy XELOX Q3W or Nivolumab 480 mg Q4W + IC Chemotherapy FOLFOX Q2W or Nivolumab 360 mg Q3W + IC Chemotherapy SOX Q3W

Arm type

Active comparator

Investigational medicinal product name

Nivolumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intravenous use

Dosage and administration details

360 mg every 3 weeks

Investigational medicinal product name

Nivolumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intravenous use

Dosage and administration details

480 mg every 4 weeks

Investigational medicinal product name

Xelox

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Oxaliplatin 130mg/m^2 Day 1 of each cycle

Investigational medicinal product name

Xelox

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Capecitabine 1000mg/m^2 twice daily Day 1 - Day 14 of each cycle

Investigational medicinal product name

Sox

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Oxaliplatin 130 mg/m^2 Day 1

Investigational medicinal product name

Folfox

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intravenous use

Dosage and administration details

Leucovorin 400 mg/m^2 Day 1

Investigational medicinal product name

Folfox

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intravenous use

Dosage and administration details

fluorouracil 400 mg/m^2 Day 1

Investigational medicinal product name

Folfox

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intravenous use

Dosage and administration details

fluorouracil 400 mg/m^2 continuous infusion for over 24 hours daily Day 1 and 2 of each cycle, every 2 weeks.

Investigational medicinal product name

Sox

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Oxaliplatin 130mg/m^2 twice daily Day 1 to 14 of each cycle, every 3 weeks

Investigational medicinal product name

Folfox

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Oxaliplatin 85mg/m^2 Day 1

Number of subjects in period 2	BMS986213 + Chemotherapy	Nivolumab + Chemotherapy
Started	136	135
Completed	0	1
Not completed	136	134
Adverse event, serious fatal	11	9
Consent withdrawn by subject	1	1
Completed Treatment	-	2
Participant no longer meets study criteria	1	-
Adverse Event unrelated to Study Drug	7	6
maximum clinical benefit	-	2
Poor/Non-compliance	1	-
Other reasons	10	8
Study Drug Toxicity	19	9
Administrative reasons by sponsor	1	-
Disease Progression	85	97

Baseline characteristics

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Reporting group title

BMS986213 + Chemotherapy

Reporting group description

BMS986213 Q3W + Investigator Choice (IC) Chemotherapy

Reporting group title

Nivolumab + Chemotherapy

Reporting group description

Nivolumab Q3W + Investigator Choice (IC) Chemotherapy

Reporting group values	BMS986213 + Chemotherapy	Nivolumab + Chemotherapy	Total
Number of subjects	138	136	274
Age categorical
Units:
Age Continuous
Units: years
arithmetic mean (standard deviation)	59.4 ( 12.1 )	61.8 ( 11.3 )	-
Sex: Female, Male
Units: Participants
Female	44	38	82
Male	94	98	192
Race/Ethnicity, Customized
Units: Subjects
White	128	122	250
Black or African American	0	1	1
Asian	5	3	8
Asian Indian	1	1	2
Chinese	0	5	5
American Indian or Alaska Native	1	0	1
Native Hawaiian or Other Pacific Islander	1	0	1
Other	2	4	6
Ethnicity (NIH/OMB)
Units: Subjects
Hispanic or Latino	17	10	27
Not Hispanic or Latino	73	80	153
Unknown or Not Reported	48	46	94

End points

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Reporting group title

BMS986213 + Chemotherapy

Reporting group description

BMS986213 Q3W + Investigator Choice (IC) Chemotherapy

Reporting group title

Nivolumab + Chemotherapy

Reporting group description

Nivolumab Q3W + Investigator Choice (IC) Chemotherapy

Reporting group title

BMS986213 + Chemotherapy

Reporting group description

BMS986213 Q3W + Investigator Choice (IC) Chemotherapy XELOX Q3W or BMS986213 Q4W + IC Chemotherapy FOLFOX Q2W or BMS986213 Q3W + IC Chemotherapy SOX Q3W

Reporting group title

Nivolumab + Chemotherapy

Reporting group description

Nivolumab 360 mg Q3W + Investigator Choice (IC) Chemotherapy XELOX Q3W or Nivolumab 480 mg Q4W + IC Chemotherapy FOLFOX Q2W or Nivolumab 360 mg Q3W + IC Chemotherapy SOX Q3W

Primary: BICR-Assessed Objective Response Rate (ORR) in Randomized LAG-3 Positive (>=1 %) Participants

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End point title

BICR-Assessed Objective Response Rate (ORR) in Randomized LAG-3 Positive (>=1 %) Participants ^[1]

End point description

The number of LAG-3 Positive (>=1%) participants with a Best Overall Response (BOR) of confirmed Complete Response (CR) or Partial Response (PR) divided by the number of randomized LAG-3 positive (>=1%) participants in each arm; recorded between randomization date and the date of objectively documented progression [per RECISIT 1.1], death due to any cause, or date of subsequent anticancer therapy, whichever occurs first. CR= Disappearance of all target lesions PR= At least a 30% decrease in the sum of diameters of target lesions

End point type

Primary

End point timeframe

Up to 25 months

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only summary table planned for this endpoint

End point values	BMS986213 + Chemotherapy	Nivolumab + Chemotherapy
Number of subjects analysed	97	98
Units: Percentage of Participants
number (confidence interval 95%)	48.5 (38.2 to 58.8)	61.2 (50.8 to 70.9)

No statistical analyses for this end point

Primary: BICR-Assessed Objective Response Rate (ORR) in Randomized LAG-3 Positive (>=1 %) Participants - Extended Collection

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End point title

BICR-Assessed Objective Response Rate (ORR) in Randomized LAG-3 Positive (>=1 %) Participants - Extended Collection ^[2]

End point description

End point type

Primary

End point timeframe

From randomization date to the date of objectively documented progression, death due to any cause, or date of subsequent anticancer therapy, whichever occurs first (Up to 63 months)

Notes
[2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only summary table planned for this endpoint

End point values	BMS986213 + Chemotherapy	Nivolumab + Chemotherapy
Number of subjects analysed	97	98
Units: Percentage of Participants
number (confidence interval 95%)	27.8 (19.2 to 37.9)	43.9 (33.9 to 54.3)

No statistical analyses for this end point

Secondary: Objective Response Rate (ORR)

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End point title

Objective Response Rate (ORR)

End point description

Objective response rate (ORR) based on Blinded Independent Central Review (BICR) and Investigator assessments is defined as the number of participants with a Best Overall Response (BOR) of confirmed Complete Response (CR) or Partial Response (PR) divided by the number of randomized participants in each arm; recorded between randomization date and the date of objectively documented progression [per RECISIT 1.1], death due to any cause, or date of subsequent anticancer therapy, whichever occurs first. CR= Disappearance of all target lesions PR= At least a 30% decrease in the sum of diameters of target lesions

End point type

Secondary

End point timeframe

From randomization date to the date of objectively documented progression, death due to any cause, or date of subsequent anticancer therapy, whichever occurs first (Up to 63 months)

End point values	BMS986213 + Chemotherapy	Nivolumab + Chemotherapy
Number of subjects analysed	138	136
Units: Percentage of participants
number (confidence interval 95%)
BICR-assessed with LAG-3 expression <1%	26.8 (14.2 to 42.9)	36.8 (21.8 to 54.0)
BICR-assessed Overall	27.5 (20.3 to 35.8)	41.9 (33.5 to 50.7)
Investigator-assessed with LAG-3 expression >=1%	53.6 (43.2 to 63.8)	54.1 (43.7 to 64.2)
Investigator-assessed with LAG-3 expression <1%	36.6 (22.1 to 53.1)	42.1 (26.3 to 59.2)
Investigator-assessed Overall	48.6 (40.0 to 57.2)	50.7 (42.0 to 59.4)

No statistical analyses for this end point

Secondary: Duration of Response (DOR)

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End point title

Duration of Response (DOR)

End point description

Duration of Response (DOR) based on Blinded Independent Central Review (BICR) and investigator is defined as the time between the date of first documented complete response (CR) or partial response (PR) and the date of the first disease progression, per RECIST 1.1, or death due to any cause, or date of subsequent anticancer therapy, whichever occurs first. CR= Disappearance of all target lesions PR= At least a 30% decrease in the sum of diameters of target lesions

End point type

Secondary

End point timeframe

From the date of first dose to the date of the first disease progression or death due to any cause, or date of subsequent anticancer therapy, whichever occurs first (Up to 63 months)

End point values	BMS986213 + Chemotherapy	Nivolumab + Chemotherapy
Number of subjects analysed	67	69
Units: Months
median (confidence interval 95%)
BICR-assessed with LAG-3 expression >=1%	7.72 (4.37 to 9.95)	10.78 (5.85 to 20.67)
BICR-assessed with LAG-3 expression <1%	5.44 (3.06 to 7.00)	5.55 (3.48 to 9.95)
BICR-assessed Overall	5.68 (5.32 to 9.63)	6.93 (5.55 to 12.25)
Investigator-assessed with LAG-3 expression >=1%	6.21 (4.47 to 7.82)	10.28 (7.06 to 15.61)
Investigator-assessed with LAG-3 expression <1%	5.54 (3.02 to 7.43)	8.31 (6.28 to 14.13)
Investigator-assessed Overall	5.88 (4.47 to 6.93)	9.92 (7.13 to 13.60)

No statistical analyses for this end point

Secondary: Overall Survival (OS)

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End point title

Overall Survival (OS)

End point description

Overall Survival (OS) is defined as the time between the date of randomization and the date of death due to any cause. For those without documentation of death, OS will be censored on the last date the participant was known to be alive.

End point type

Secondary

End point timeframe

From the date of randomization to the date of death due to any cause (Up to 63 months)

End point values	BMS986213 + Chemotherapy	Nivolumab + Chemotherapy
Number of subjects analysed	138	136
Units: Months
median (confidence interval 95%)
LAG-3 Expression >=1%	14.19 (11.89 to 18.56)	14.98 (10.02 to 21.98)
LAG-3 Expression <1%	9.72 (6.64 to 12.75)	15.51 (11.43 to 17.61)
Overall	12.65 (10.91 to 14.49)	15.15 (11.50 to 17.61)

No statistical analyses for this end point

Secondary: Progression-Free Survival (PFS)

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End point title

Progression-Free Survival (PFS)

End point description

Progression-Free Survival (PFS) per Blinded Independent Central Review (BICR) and Investigator is defined as the time between the date of randomization and the first date of documented progression, or death due to any cause, or date of subsequent anticancer therapy, whichever occurs first. Participants who die without a reported prior progression (and die without start of subsequent therapy) will be considered to have progressed on the date of death. Progression=At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study and the sum must also demonstrate an absolute increase of at least 5 mm.

End point type

Secondary

End point timeframe

From the date of randomization to the first date of documented progression, or death due to any cause, or date of subsequent anticancer therapy, whichever occurs first (Up to 63 months)

End point values	BMS986213 + Chemotherapy	Nivolumab + Chemotherapy
Number of subjects analysed	138	136
Units: Months
median (confidence interval 95%)
BICR-assessed LAG-3 Expression >=1%	7.26 (6.64 to 11.07)	10.84 (7.43 to 15.70)
BICR-assessed LAG-3 Expression <1%	6.80 (5.98 to 8.80)	10.45 (6.11 to 13.70)
BICR-assessed Overall	7.13 (6.74 to 9.82)	10.45 (7.13 to 12.65)
Investigator-assessed LAG-3 Expression >=1%	6.97 (5.78 to 8.34)	8.31 (5.88 to 9.72)
Investigator-assessed LAG-3 Expression <1%	5.39 (4.37 to 7.98)	9.69 (6.87 to 13.70)
Investigator-assessed Overall	6.64 (5.52 to 7.62)	8.31 (6.90 to 11.04)

No statistical analyses for this end point

Secondary: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)

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End point title

Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)

End point description

Number of participants with any grade adverse events (AEs), serious adverse events (SAE), and adverse events leading to discontinuation using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE v 5.0). An AE is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life threatening, requires inpatient hospitalization, results in significant disability, is a birth defect, or is an important medical event.

End point type

Secondary

End point timeframe

From first dose to 30 days post last dose (Up to 60 months)

End point values	BMS986213 + Chemotherapy	Nivolumab + Chemotherapy
Number of subjects analysed	136	135
Units: Participants
Adverse Events (AEs)	135	135
Serious Adverse Events (SAEs)	99	87
Adverse Events leading to discontinuation	76	56

No statistical analyses for this end point

Secondary: Number of Participants who Died

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End point title

Number of Participants who Died

End point description

Number of participants who died in each arm.

End point type

Secondary

End point timeframe

Up to 63 months

End point values	BMS986213 + Chemotherapy	Nivolumab + Chemotherapy
Number of subjects analysed	136	135
Units: Participants	122	118

No statistical analyses for this end point

Secondary: Number of Participants with Laboratory Abnormalities in Specific Liver Tests

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End point title

Number of Participants with Laboratory Abnormalities in Specific Liver Tests

End point description

Number of participants with laboratory abnormalities in specific liver tests based on US conventional units. The number of participants with the following laboratory abnormalities from on-treatment evaluations will be summarized: - ALT or AST > 3 x ULN, > 5 x ULN, > 10 x ULN and > 20 x ULN - Total bilirubin > 2 x ULN - ALP > 1.5 x ULN - Concurrent (within 1 day) ALT or AST > 3 x ULN and total bilirubin > 1.5 x ULN - Concurrent (within 30 days) ALT or AST > 3 x ULN and total bilirubin > 1.5 x ULN - Concurrent (within 1 day) ALT or AST > 3 x ULN and total bilirubin > 2 x ULN - Concurrent (within 30 days) ALT or AST > 3 x ULN and total bilirubin > 2 x ULN

End point type

Secondary

End point timeframe

From first dose to 30 days post last dose (Up to 60 months)

End point values	BMS986213 + Chemotherapy	Nivolumab + Chemotherapy
Number of subjects analysed	129	134
Units: Participants
ALT or AST > 3xULN	31	14
ALT or AST > 5xULN	12	5
ALT or AST > 10xULN	4	1
ALT or AST > 20xULN	2	0
TOTAL BILIRUBIN > 2xULN	6	3
ALP > 1.5xULN	50	56
ALT/AST>3xULN BILIRUBIN>1.5xULN w/n 1 DAY	5	2
ALT/AST>3xULN WITH BILIRUBIN>1.5xULN w/n 30 DAYS	5	2
ALT/AST>3xULN WITH BILIRUBIN>2xULN w/n 1 DAY	4	2
ALT/AST>3xULN WITH BILIRUBIN>2xULN w/n 30 DAYS	4	2

No statistical analyses for this end point

Secondary: Number of Participants with Laboratory Abnormalities in Specific Thyroid Tests

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End point title

Number of Participants with Laboratory Abnormalities in Specific Thyroid Tests

End point description

Number of participants with laboratory abnormalities in specific thyroid tests based on US conventional units. The number of participants with the following laboratory abnormalities from on-treatment evaluations will be summarized: - TSH value > ULN and - with baseline TSH value <= ULN - with at least one FT3/FT4 test value < LLN within 2-week window after the abnormal TSH test - with all FT3/FT4 test values >= LLN within 2-week window after the abnormal TSH test - with FT3/FT4 missing within 2-week window after the abnormal TSH test. - TSH < LLN and - with baseline TSH value >= LLN - with at least one FT3/FT4 test value > ULN within 2-week window after the abnormal TSH test - with all FT3/FT4 test values <= ULN within 2-week window after the abnormal TSH test - with FT3/FT4 missing within 2-week window after the abnormal TSH test

End point type

Secondary

End point timeframe

From first dose to 30 days post last dose (Up to 60 months)

End point values	BMS986213 + Chemotherapy	Nivolumab + Chemotherapy
Number of subjects analysed	129	133
Units: Participants
TSH > ULN	39	43
TSH > ULN WITH TSH <= ULN AT BASELINE	35	33
TSH>ULN WITH AT LEAST 1 FT3/FT4<LLN	24	20
TSH>ULN WITH ALL OTHER FT3/FT4>= LLN	15	19
TSH>ULN WITH FT3/FT4 TEST MISSING	18	24
TSH < LLN	42	26
TSH < LLN WITH TSH >= LLN AT BASELINE	40	22
TSH<LLN WITH AT LEAST FT3/FT4>ULN	22	11
TSH<LLN WITH ALL OTHER FT3/FT4<=ULN	12	10
TSH<LLN WITH FT3/FT4 TEST MISSING	19	11

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 63 months). SAEs and Other AEs were assessed from first dose up to 100 days post last dose (Up to approximately 63 months).

Adverse event reporting additional description

The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

26.1

Reporting group title

Nivolumab + Chemotherapy

Reporting group description

Nivolumab Q3W + Investigator Choice (IC) Chemotherapy

Reporting group title

BMS986213 + Chemotherapy

Reporting group description

BMS986213 Q3W + Investigator Choice (IC) Chemotherapy

Serious adverse events	Nivolumab + Chemotherapy	BMS986213 + Chemotherapy
Total subjects affected by serious adverse events
subjects affected / exposed	100 / 135 (74.07%)	110 / 136 (80.88%)
number of deaths (all causes)	118	122
number of deaths resulting from adverse events	43	45
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Gastric cancer
subjects affected / exposed	1 / 135 (0.74%)	1 / 136 (0.74%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Bladder transitional cell carcinoma
subjects affected / exposed	1 / 135 (0.74%)	0 / 136 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Adenocarcinoma
subjects affected / exposed	0 / 135 (0.00%)	1 / 136 (0.74%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Abdominal wall neoplasm
subjects affected / exposed	1 / 135 (0.74%)	0 / 136 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Infected neoplasm
subjects affected / exposed	0 / 135 (0.00%)	1 / 136 (0.74%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Lymphangiosis carcinomatosa
subjects affected / exposed	1 / 135 (0.74%)	1 / 136 (0.74%)
occurrences causally related to treatment / all	0 / 1	1 / 1
deaths causally related to treatment / all	0 / 0	1 / 1
Malignant neoplasm progression
subjects affected / exposed	26 / 135 (19.26%)	30 / 136 (22.06%)
occurrences causally related to treatment / all	0 / 27	0 / 30
deaths causally related to treatment / all	25 / 25	26 / 26
Metastases to central nervous system
subjects affected / exposed	1 / 135 (0.74%)	1 / 136 (0.74%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Metastases to liver
subjects affected / exposed	0 / 135 (0.00%)	2 / 136 (1.47%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Metastases to meninges
subjects affected / exposed	2 / 135 (1.48%)	0 / 136 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	1 / 1	0 / 0
Metastases to skin
subjects affected / exposed	0 / 135 (0.00%)	1 / 136 (0.74%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Metastatic gastric cancer
subjects affected / exposed	1 / 135 (0.74%)	0 / 136 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Neuroendocrine tumour
subjects affected / exposed	1 / 135 (0.74%)	0 / 136 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Ovarian neoplasm
subjects affected / exposed	0 / 135 (0.00%)	1 / 136 (0.74%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Tumour haemorrhage
subjects affected / exposed	0 / 135 (0.00%)	3 / 136 (2.21%)
occurrences causally related to treatment / all	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	2 / 2
Tumour pain
subjects affected / exposed	0 / 135 (0.00%)	1 / 136 (0.74%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Tumour perforation
subjects affected / exposed	1 / 135 (0.74%)	0 / 136 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Vascular disorders
Venous thrombosis limb
subjects affected / exposed	0 / 135 (0.00%)	1 / 136 (0.74%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Embolism
subjects affected / exposed	0 / 135 (0.00%)	2 / 136 (1.47%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Hypertension
subjects affected / exposed	1 / 135 (0.74%)	1 / 136 (0.74%)
occurrences causally related to treatment / all	1 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Hypotension
subjects affected / exposed	2 / 135 (1.48%)	3 / 136 (2.21%)
occurrences causally related to treatment / all	1 / 2	3 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Pelvic venous thrombosis
subjects affected / exposed	0 / 135 (0.00%)	1 / 136 (0.74%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Thrombosis
subjects affected / exposed	1 / 135 (0.74%)	0 / 136 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
General disorders and administration site conditions
Influenza like illness
subjects affected / exposed	0 / 135 (0.00%)	1 / 136 (0.74%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Asthenia
subjects affected / exposed	1 / 135 (0.74%)	0 / 136 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Chest pain
subjects affected / exposed	0 / 135 (0.00%)	1 / 136 (0.74%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Disease progression
subjects affected / exposed	0 / 135 (0.00%)	1 / 136 (0.74%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	1 / 1
Fatigue
subjects affected / exposed	2 / 135 (1.48%)	3 / 136 (2.21%)
occurrences causally related to treatment / all	1 / 2	1 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
General physical health deterioration
subjects affected / exposed	6 / 135 (4.44%)	3 / 136 (2.21%)
occurrences causally related to treatment / all	1 / 7	0 / 3
deaths causally related to treatment / all	4 / 4	0 / 0
Medical device pain
subjects affected / exposed	1 / 135 (0.74%)	0 / 136 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pyrexia
subjects affected / exposed	7 / 135 (5.19%)	12 / 136 (8.82%)
occurrences causally related to treatment / all	1 / 10	5 / 15
deaths causally related to treatment / all	0 / 0	0 / 0
Pain
subjects affected / exposed	1 / 135 (0.74%)	1 / 136 (0.74%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Immune system disorders
Contrast media reaction
subjects affected / exposed	0 / 135 (0.00%)	1 / 136 (0.74%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Hypersensitivity
subjects affected / exposed	0 / 135 (0.00%)	1 / 136 (0.74%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Immune-mediated lung disease
subjects affected / exposed	1 / 135 (0.74%)	0 / 136 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Dyspnoea
subjects affected / exposed	3 / 135 (2.22%)	1 / 136 (0.74%)
occurrences causally related to treatment / all	0 / 3	0 / 1
deaths causally related to treatment / all	1 / 1	0 / 0
Lung disorder
subjects affected / exposed	0 / 135 (0.00%)	1 / 136 (0.74%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Organising pneumonia
subjects affected / exposed	1 / 135 (0.74%)	0 / 136 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pleural effusion
subjects affected / exposed	6 / 135 (4.44%)	6 / 136 (4.41%)
occurrences causally related to treatment / all	0 / 8	0 / 7
deaths causally related to treatment / all	0 / 0	1 / 1
Pneumonitis
subjects affected / exposed	7 / 135 (5.19%)	1 / 136 (0.74%)
occurrences causally related to treatment / all	8 / 8	1 / 1
deaths causally related to treatment / all	1 / 1	0 / 0
Pulmonary embolism
subjects affected / exposed	1 / 135 (0.74%)	3 / 136 (2.21%)
occurrences causally related to treatment / all	0 / 1	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Respiratory failure
subjects affected / exposed	1 / 135 (0.74%)	2 / 136 (1.47%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	1 / 1	2 / 2
Psychiatric disorders
Confusional state
subjects affected / exposed	2 / 135 (1.48%)	1 / 136 (0.74%)
occurrences causally related to treatment / all	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Product issues
Device dislocation
subjects affected / exposed	2 / 135 (1.48%)	0 / 136 (0.00%)
occurrences causally related to treatment / all	0 / 4	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Device malfunction
subjects affected / exposed	0 / 135 (0.00%)	1 / 136 (0.74%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Investigations
Blood creatinine increased
subjects affected / exposed	0 / 135 (0.00%)	1 / 136 (0.74%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Blood creatine phosphokinase increased
subjects affected / exposed	0 / 135 (0.00%)	1 / 136 (0.74%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Blood bilirubin increased
subjects affected / exposed	1 / 135 (0.74%)	1 / 136 (0.74%)
occurrences causally related to treatment / all	0 / 2	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Aspartate aminotransferase increased
subjects affected / exposed	0 / 135 (0.00%)	2 / 136 (1.47%)
occurrences causally related to treatment / all	0 / 0	2 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Alanine aminotransferase increased
subjects affected / exposed	0 / 135 (0.00%)	1 / 136 (0.74%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
General physical condition abnormal
subjects affected / exposed	0 / 135 (0.00%)	1 / 136 (0.74%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Platelet count decreased
subjects affected / exposed	0 / 135 (0.00%)	1 / 136 (0.74%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Neutrophil count decreased
subjects affected / exposed	0 / 135 (0.00%)	1 / 136 (0.74%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Liver function test increased
subjects affected / exposed	0 / 135 (0.00%)	1 / 136 (0.74%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Liver function test abnormal
subjects affected / exposed	0 / 135 (0.00%)	1 / 136 (0.74%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Hepatic enzyme increased
subjects affected / exposed	0 / 135 (0.00%)	1 / 136 (0.74%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Haemoglobin decreased
subjects affected / exposed	0 / 135 (0.00%)	1 / 136 (0.74%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Injury, poisoning and procedural complications
Overdose
subjects affected / exposed	1 / 135 (0.74%)	0 / 136 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Craniocerebral injury
subjects affected / exposed	1 / 135 (0.74%)	0 / 136 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Fall
subjects affected / exposed	0 / 135 (0.00%)	1 / 136 (0.74%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Femoral neck fracture
subjects affected / exposed	0 / 135 (0.00%)	1 / 136 (0.74%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Humerus fracture
subjects affected / exposed	1 / 135 (0.74%)	0 / 136 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Infusion related reaction
subjects affected / exposed	0 / 135 (0.00%)	5 / 136 (3.68%)
occurrences causally related to treatment / all	0 / 0	5 / 6
deaths causally related to treatment / all	0 / 0	0 / 0
Subdural haemorrhage
subjects affected / exposed	1 / 135 (0.74%)	0 / 136 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Spinal compression fracture
subjects affected / exposed	0 / 135 (0.00%)	1 / 136 (0.74%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Post procedural complication
subjects affected / exposed	0 / 135 (0.00%)	1 / 136 (0.74%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Cardiac disorders
Angina pectoris
subjects affected / exposed	1 / 135 (0.74%)	1 / 136 (0.74%)
occurrences causally related to treatment / all	1 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Acute coronary syndrome
subjects affected / exposed	1 / 135 (0.74%)	0 / 136 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Arrhythmia
subjects affected / exposed	0 / 135 (0.00%)	1 / 136 (0.74%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Atrial fibrillation
subjects affected / exposed	2 / 135 (1.48%)	1 / 136 (0.74%)
occurrences causally related to treatment / all	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Atrioventricular block
subjects affected / exposed	0 / 135 (0.00%)	1 / 136 (0.74%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Cardiac failure
subjects affected / exposed	1 / 135 (0.74%)	0 / 136 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Cardiac failure acute
subjects affected / exposed	1 / 135 (0.74%)	0 / 136 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Coronary artery disease
subjects affected / exposed	1 / 135 (0.74%)	0 / 136 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Myocardial infarction
subjects affected / exposed	0 / 135 (0.00%)	1 / 136 (0.74%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Myocarditis
subjects affected / exposed	2 / 135 (1.48%)	0 / 136 (0.00%)
occurrences causally related to treatment / all	2 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pericarditis
subjects affected / exposed	1 / 135 (0.74%)	0 / 136 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Right ventricular failure
subjects affected / exposed	0 / 135 (0.00%)	1 / 136 (0.74%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Arteriospasm coronary
subjects affected / exposed	0 / 135 (0.00%)	1 / 136 (0.74%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Nervous system disorders
Encephalitis autoimmune
subjects affected / exposed	0 / 135 (0.00%)	2 / 136 (1.47%)
occurrences causally related to treatment / all	0 / 0	2 / 2
deaths causally related to treatment / all	0 / 0	1 / 1
Guillain-Barre syndrome
subjects affected / exposed	0 / 135 (0.00%)	1 / 136 (0.74%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Axonal neuropathy
subjects affected / exposed	0 / 135 (0.00%)	1 / 136 (0.74%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Cerebrovascular accident
subjects affected / exposed	0 / 135 (0.00%)	2 / 136 (1.47%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Ischaemic stroke
subjects affected / exposed	1 / 135 (0.74%)	0 / 136 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Sciatica
subjects affected / exposed	1 / 135 (0.74%)	0 / 136 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Spinal cord compression
subjects affected / exposed	0 / 135 (0.00%)	1 / 136 (0.74%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Syncope
subjects affected / exposed	2 / 135 (1.48%)	1 / 136 (0.74%)
occurrences causally related to treatment / all	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Presyncope
subjects affected / exposed	1 / 135 (0.74%)	0 / 136 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	7 / 135 (5.19%)	2 / 136 (1.47%)
occurrences causally related to treatment / all	2 / 8	1 / 2
deaths causally related to treatment / all	1 / 1	0 / 0
Febrile neutropenia
subjects affected / exposed	2 / 135 (1.48%)	5 / 136 (3.68%)
occurrences causally related to treatment / all	2 / 2	5 / 5
deaths causally related to treatment / all	0 / 0	0 / 0
Immune thrombocytopenia
subjects affected / exposed	0 / 135 (0.00%)	1 / 136 (0.74%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Thrombocytopenia
subjects affected / exposed	0 / 135 (0.00%)	1 / 136 (0.74%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Thrombotic microangiopathy
subjects affected / exposed	0 / 135 (0.00%)	2 / 136 (1.47%)
occurrences causally related to treatment / all	0 / 0	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Neutropenia
subjects affected / exposed	1 / 135 (0.74%)	1 / 136 (0.74%)
occurrences causally related to treatment / all	1 / 1	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Ear and labyrinth disorders
Vestibular disorder
subjects affected / exposed	0 / 135 (0.00%)	1 / 136 (0.74%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Eye disorders
Diplopia
subjects affected / exposed	1 / 135 (0.74%)	0 / 136 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Blindness unilateral
subjects affected / exposed	0 / 135 (0.00%)	1 / 136 (0.74%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Gastrointestinal disorders
Gastrointestinal haemorrhage
subjects affected / exposed	3 / 135 (2.22%)	1 / 136 (0.74%)
occurrences causally related to treatment / all	0 / 3	0 / 1
deaths causally related to treatment / all	1 / 1	1 / 1
Abdominal hernia
subjects affected / exposed	0 / 135 (0.00%)	1 / 136 (0.74%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Abdominal pain
subjects affected / exposed	8 / 135 (5.93%)	6 / 136 (4.41%)
occurrences causally related to treatment / all	1 / 9	0 / 9
deaths causally related to treatment / all	0 / 0	0 / 0
Abdominal pain lower
subjects affected / exposed	1 / 135 (0.74%)	0 / 136 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Abdominal pain upper
subjects affected / exposed	3 / 135 (2.22%)	0 / 136 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Ascites
subjects affected / exposed	3 / 135 (2.22%)	1 / 136 (0.74%)
occurrences causally related to treatment / all	0 / 3	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Colitis
subjects affected / exposed	2 / 135 (1.48%)	3 / 136 (2.21%)
occurrences causally related to treatment / all	3 / 3	3 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Constipation
subjects affected / exposed	2 / 135 (1.48%)	1 / 136 (0.74%)
occurrences causally related to treatment / all	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Diarrhoea
subjects affected / exposed	8 / 135 (5.93%)	3 / 136 (2.21%)
occurrences causally related to treatment / all	8 / 10	4 / 4
deaths causally related to treatment / all	0 / 0	0 / 0
Dysphagia
subjects affected / exposed	9 / 135 (6.67%)	4 / 136 (2.94%)
occurrences causally related to treatment / all	0 / 9	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0
Enterocolitis
subjects affected / exposed	1 / 135 (0.74%)	0 / 136 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Enterocolitis haemorrhagic
subjects affected / exposed	1 / 135 (0.74%)	0 / 136 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Faeces discoloured
subjects affected / exposed	0 / 135 (0.00%)	1 / 136 (0.74%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Gastric haemorrhage
subjects affected / exposed	0 / 135 (0.00%)	3 / 136 (2.21%)
occurrences causally related to treatment / all	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	1 / 1
Gastrointestinal inflammation
subjects affected / exposed	0 / 135 (0.00%)	1 / 136 (0.74%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Oesophageal obstruction
subjects affected / exposed	0 / 135 (0.00%)	2 / 136 (1.47%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Haematemesis
subjects affected / exposed	3 / 135 (2.22%)	2 / 136 (1.47%)
occurrences causally related to treatment / all	0 / 4	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Haematochezia
subjects affected / exposed	1 / 135 (0.74%)	0 / 136 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Haemorrhoidal haemorrhage
subjects affected / exposed	1 / 135 (0.74%)	0 / 136 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Ileus
subjects affected / exposed	2 / 135 (1.48%)	1 / 136 (0.74%)
occurrences causally related to treatment / all	0 / 2	0 / 1
deaths causally related to treatment / all	1 / 1	0 / 0
Immune-mediated enterocolitis
subjects affected / exposed	1 / 135 (0.74%)	1 / 136 (0.74%)
occurrences causally related to treatment / all	1 / 1	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Intestinal obstruction
subjects affected / exposed	8 / 135 (5.93%)	1 / 136 (0.74%)
occurrences causally related to treatment / all	0 / 9	0 / 1
deaths causally related to treatment / all	2 / 2	0 / 0
Intestinal perforation
subjects affected / exposed	0 / 135 (0.00%)	1 / 136 (0.74%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	1 / 1
Large intestinal obstruction
subjects affected / exposed	1 / 135 (0.74%)	0 / 136 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Large intestine perforation
subjects affected / exposed	0 / 135 (0.00%)	1 / 136 (0.74%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Melaena
subjects affected / exposed	0 / 135 (0.00%)	3 / 136 (2.21%)
occurrences causally related to treatment / all	0 / 0	1 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Nausea
subjects affected / exposed	6 / 135 (4.44%)	2 / 136 (1.47%)
occurrences causally related to treatment / all	5 / 7	2 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Obstruction gastric
subjects affected / exposed	1 / 135 (0.74%)	1 / 136 (0.74%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Oesophageal fistula
subjects affected / exposed	0 / 135 (0.00%)	1 / 136 (0.74%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Gastrooesophageal reflux disease
subjects affected / exposed	1 / 135 (0.74%)	0 / 136 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Oesophageal pain
subjects affected / exposed	0 / 135 (0.00%)	1 / 136 (0.74%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Oesophageal ulcer
subjects affected / exposed	0 / 135 (0.00%)	1 / 136 (0.74%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pancreatitis acute
subjects affected / exposed	1 / 135 (0.74%)	0 / 136 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Proctalgia
subjects affected / exposed	1 / 135 (0.74%)	0 / 136 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Small intestinal obstruction
subjects affected / exposed	1 / 135 (0.74%)	2 / 136 (1.47%)
occurrences causally related to treatment / all	0 / 1	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Small intestinal stenosis
subjects affected / exposed	1 / 135 (0.74%)	0 / 136 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Stomatitis
subjects affected / exposed	0 / 135 (0.00%)	2 / 136 (1.47%)
occurrences causally related to treatment / all	0 / 0	2 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Upper gastrointestinal haemorrhage
subjects affected / exposed	1 / 135 (0.74%)	1 / 136 (0.74%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Vomiting
subjects affected / exposed	7 / 135 (5.19%)	3 / 136 (2.21%)
occurrences causally related to treatment / all	3 / 8	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Oesophageal perforation
subjects affected / exposed	0 / 135 (0.00%)	2 / 136 (1.47%)
occurrences causally related to treatment / all	0 / 0	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Hepatobiliary disorders
Jaundice cholestatic
subjects affected / exposed	1 / 135 (0.74%)	0 / 136 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	1 / 1	0 / 0
Autoimmune hepatitis
subjects affected / exposed	1 / 135 (0.74%)	1 / 136 (0.74%)
occurrences causally related to treatment / all	1 / 1	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Biliary colic
subjects affected / exposed	0 / 135 (0.00%)	1 / 136 (0.74%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Cholangitis
subjects affected / exposed	1 / 135 (0.74%)	0 / 136 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Cholecystitis
subjects affected / exposed	0 / 135 (0.00%)	1 / 136 (0.74%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Gallbladder obstruction
subjects affected / exposed	0 / 135 (0.00%)	1 / 136 (0.74%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Hepatic failure
subjects affected / exposed	0 / 135 (0.00%)	1 / 136 (0.74%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	1 / 1
Hepatitis
subjects affected / exposed	1 / 135 (0.74%)	2 / 136 (1.47%)
occurrences causally related to treatment / all	1 / 1	3 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Hepatitis acute
subjects affected / exposed	0 / 135 (0.00%)	1 / 136 (0.74%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Hepatobiliary disease
subjects affected / exposed	1 / 135 (0.74%)	0 / 136 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Hyperbilirubinaemia
subjects affected / exposed	1 / 135 (0.74%)	0 / 136 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Hypertransaminasaemia
subjects affected / exposed	0 / 135 (0.00%)	1 / 136 (0.74%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Immune-mediated hepatitis
subjects affected / exposed	1 / 135 (0.74%)	0 / 136 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
Rash
subjects affected / exposed	1 / 135 (0.74%)	0 / 136 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Renal and urinary disorders
Acute kidney injury
subjects affected / exposed	2 / 135 (1.48%)	5 / 136 (3.68%)
occurrences causally related to treatment / all	2 / 2	4 / 5
deaths causally related to treatment / all	1 / 1	1 / 1
Hydronephrosis
subjects affected / exposed	0 / 135 (0.00%)	1 / 136 (0.74%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Nephropathy toxic
subjects affected / exposed	1 / 135 (0.74%)	1 / 136 (0.74%)
occurrences causally related to treatment / all	1 / 1	2 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Renal failure
subjects affected / exposed	2 / 135 (1.48%)	0 / 136 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Renal tubular necrosis
subjects affected / exposed	1 / 135 (0.74%)	0 / 136 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Urinary incontinence
subjects affected / exposed	0 / 135 (0.00%)	1 / 136 (0.74%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Urinary tract obstruction
subjects affected / exposed	0 / 135 (0.00%)	1 / 136 (0.74%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Endocrine disorders
Immune-mediated hypophysitis
subjects affected / exposed	0 / 135 (0.00%)	2 / 136 (1.47%)
occurrences causally related to treatment / all	0 / 0	2 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Adrenal insufficiency
subjects affected / exposed	0 / 135 (0.00%)	2 / 136 (1.47%)
occurrences causally related to treatment / all	0 / 0	2 / 2
deaths causally related to treatment / all	0 / 0	1 / 1
Autoimmune thyroiditis
subjects affected / exposed	0 / 135 (0.00%)	1 / 136 (0.74%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Glucocorticoid deficiency
subjects affected / exposed	1 / 135 (0.74%)	0 / 136 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Hypophysitis
subjects affected / exposed	0 / 135 (0.00%)	1 / 136 (0.74%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Lymphocytic hypophysitis
subjects affected / exposed	0 / 135 (0.00%)	1 / 136 (0.74%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Myositis
subjects affected / exposed	0 / 135 (0.00%)	1 / 136 (0.74%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Intervertebral disc protrusion
subjects affected / exposed	1 / 135 (0.74%)	0 / 136 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Bone pain
subjects affected / exposed	0 / 135 (0.00%)	1 / 136 (0.74%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Back pain
subjects affected / exposed	1 / 135 (0.74%)	2 / 136 (1.47%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Infections and infestations
Acute sinusitis
subjects affected / exposed	0 / 135 (0.00%)	1 / 136 (0.74%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Adrenalitis
subjects affected / exposed	0 / 135 (0.00%)	2 / 136 (1.47%)
occurrences causally related to treatment / all	0 / 0	2 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Appendicitis
subjects affected / exposed	1 / 135 (0.74%)	0 / 136 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Bronchitis
subjects affected / exposed	1 / 135 (0.74%)	1 / 136 (0.74%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
COVID-19 pneumonia
subjects affected / exposed	2 / 135 (1.48%)	2 / 136 (1.47%)
occurrences causally related to treatment / all	0 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Cholangitis infective
subjects affected / exposed	0 / 135 (0.00%)	1 / 136 (0.74%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Device related infection
subjects affected / exposed	1 / 135 (0.74%)	2 / 136 (1.47%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Enterobacter sepsis
subjects affected / exposed	0 / 135 (0.00%)	1 / 136 (0.74%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Enterocolitis infectious
subjects affected / exposed	1 / 135 (0.74%)	1 / 136 (0.74%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Febrile infection
subjects affected / exposed	1 / 135 (0.74%)	0 / 136 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Gastroenteritis
subjects affected / exposed	2 / 135 (1.48%)	0 / 136 (0.00%)
occurrences causally related to treatment / all	1 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Infection
subjects affected / exposed	1 / 135 (0.74%)	4 / 136 (2.94%)
occurrences causally related to treatment / all	0 / 1	3 / 4
deaths causally related to treatment / all	0 / 0	0 / 0
Influenza
subjects affected / exposed	2 / 135 (1.48%)	0 / 136 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Kidney infection
subjects affected / exposed	0 / 135 (0.00%)	1 / 136 (0.74%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Large intestine infection
subjects affected / exposed	1 / 135 (0.74%)	0 / 136 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Oral candidiasis
subjects affected / exposed	0 / 135 (0.00%)	1 / 136 (0.74%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Upper respiratory tract infection
subjects affected / exposed	0 / 135 (0.00%)	2 / 136 (1.47%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Sepsis
subjects affected / exposed	2 / 135 (1.48%)	7 / 136 (5.15%)
occurrences causally related to treatment / all	2 / 3	3 / 8
deaths causally related to treatment / all	0 / 0	1 / 1
Rash pustular
subjects affected / exposed	0 / 135 (0.00%)	1 / 136 (0.74%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pyelonephritis acute
subjects affected / exposed	1 / 135 (0.74%)	0 / 136 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Post procedural infection
subjects affected / exposed	0 / 135 (0.00%)	1 / 136 (0.74%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pneumonia aspiration
subjects affected / exposed	2 / 135 (1.48%)	0 / 136 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	1 / 1	0 / 0
Pneumonia
subjects affected / exposed	8 / 135 (5.93%)	7 / 136 (5.15%)
occurrences causally related to treatment / all	1 / 9	1 / 7
deaths causally related to treatment / all	2 / 2	4 / 4
Urinary tract infection
subjects affected / exposed	1 / 135 (0.74%)	1 / 136 (0.74%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Vascular device infection
subjects affected / exposed	2 / 135 (1.48%)	1 / 136 (0.74%)
occurrences causally related to treatment / all	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Suspected COVID-19
subjects affected / exposed	1 / 135 (0.74%)	0 / 136 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Metabolism and nutrition disorders
Dehydration
subjects affected / exposed	3 / 135 (2.22%)	3 / 136 (2.21%)
occurrences causally related to treatment / all	1 / 3	1 / 4
deaths causally related to treatment / all	0 / 0	0 / 0
Decreased appetite
subjects affected / exposed	5 / 135 (3.70%)	1 / 136 (0.74%)
occurrences causally related to treatment / all	0 / 7	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Diabetes mellitus
subjects affected / exposed	1 / 135 (0.74%)	0 / 136 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Diabetic ketoacidosis
subjects affected / exposed	0 / 135 (0.00%)	1 / 136 (0.74%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Hyperglycaemia
subjects affected / exposed	1 / 135 (0.74%)	1 / 136 (0.74%)
occurrences causally related to treatment / all	4 / 4	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Hypokalaemia
subjects affected / exposed	3 / 135 (2.22%)	0 / 136 (0.00%)
occurrences causally related to treatment / all	2 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Hypophosphataemia
subjects affected / exposed	1 / 135 (0.74%)	0 / 136 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Ketoacidosis
subjects affected / exposed	1 / 135 (0.74%)	0 / 136 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Type 1 diabetes mellitus
subjects affected / exposed	0 / 135 (0.00%)	2 / 136 (1.47%)
occurrences causally related to treatment / all	0 / 0	2 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Diabetes mellitus inadequate control
subjects affected / exposed	1 / 135 (0.74%)	0 / 136 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Nivolumab + Chemotherapy	BMS986213 + Chemotherapy
Total subjects affected by non serious adverse events
subjects affected / exposed	133 / 135 (98.52%)	130 / 136 (95.59%)
Vascular disorders
Hypertension
subjects affected / exposed	15 / 135 (11.11%)	8 / 136 (5.88%)
occurrences all number	18	10
Hypotension
subjects affected / exposed	7 / 135 (5.19%)	7 / 136 (5.15%)
occurrences all number	10	7
General disorders and administration site conditions
Oedema peripheral
subjects affected / exposed	18 / 135 (13.33%)	17 / 136 (12.50%)
occurrences all number	19	19
Pyrexia
subjects affected / exposed	19 / 135 (14.07%)	33 / 136 (24.26%)
occurrences all number	28	51
Non-cardiac chest pain
subjects affected / exposed	9 / 135 (6.67%)	10 / 136 (7.35%)
occurrences all number	10	10
Mucosal inflammation
subjects affected / exposed	12 / 135 (8.89%)	16 / 136 (11.76%)
occurrences all number	13	20
General physical health deterioration
subjects affected / exposed	7 / 135 (5.19%)	2 / 136 (1.47%)
occurrences all number	8	2
Fatigue
subjects affected / exposed	70 / 135 (51.85%)	72 / 136 (52.94%)
occurrences all number	93	97
Chills
subjects affected / exposed	6 / 135 (4.44%)	8 / 136 (5.88%)
occurrences all number	6	8
Asthenia
subjects affected / exposed	21 / 135 (15.56%)	16 / 136 (11.76%)
occurrences all number	36	23
Immune system disorders
Hypersensitivity
subjects affected / exposed	3 / 135 (2.22%)	8 / 136 (5.88%)
occurrences all number	5	16
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	23 / 135 (17.04%)	28 / 136 (20.59%)
occurrences all number	26	33
Dyspnoea
subjects affected / exposed	16 / 135 (11.85%)	23 / 136 (16.91%)
occurrences all number	17	24
Epistaxis
subjects affected / exposed	10 / 135 (7.41%)	6 / 136 (4.41%)
occurrences all number	10	6
Oropharyngeal pain
subjects affected / exposed	5 / 135 (3.70%)	8 / 136 (5.88%)
occurrences all number	5	8
Pneumonitis
subjects affected / exposed	5 / 135 (3.70%)	8 / 136 (5.88%)
occurrences all number	7	8
Pulmonary embolism
subjects affected / exposed	7 / 135 (5.19%)	2 / 136 (1.47%)
occurrences all number	7	2
Rhinorrhoea
subjects affected / exposed	3 / 135 (2.22%)	7 / 136 (5.15%)
occurrences all number	3	7
Psychiatric disorders
Depression
subjects affected / exposed	8 / 135 (5.93%)	4 / 136 (2.94%)
occurrences all number	9	4
Insomnia
subjects affected / exposed	14 / 135 (10.37%)	18 / 136 (13.24%)
occurrences all number	14	21
Investigations
Alanine aminotransferase increased
subjects affected / exposed	16 / 135 (11.85%)	15 / 136 (11.03%)
occurrences all number	19	19
Aspartate aminotransferase increased
subjects affected / exposed	16 / 135 (11.85%)	18 / 136 (13.24%)
occurrences all number	20	25
Blood alkaline phosphatase increased
subjects affected / exposed	7 / 135 (5.19%)	10 / 136 (7.35%)
occurrences all number	9	10
Gamma-glutamyltransferase increased
subjects affected / exposed	8 / 135 (5.93%)	9 / 136 (6.62%)
occurrences all number	12	10
Neutrophil count decreased
subjects affected / exposed	16 / 135 (11.85%)	25 / 136 (18.38%)
occurrences all number	21	41
Platelet count decreased
subjects affected / exposed	23 / 135 (17.04%)	15 / 136 (11.03%)
occurrences all number	38	25
Weight decreased
subjects affected / exposed	21 / 135 (15.56%)	13 / 136 (9.56%)
occurrences all number	22	15
White blood cell count decreased
subjects affected / exposed	6 / 135 (4.44%)	9 / 136 (6.62%)
occurrences all number	11	14
Injury, poisoning and procedural complications
Infusion related reaction
subjects affected / exposed	11 / 135 (8.15%)	19 / 136 (13.97%)
occurrences all number	11	27
Nervous system disorders
Cold dysaesthesia
subjects affected / exposed	8 / 135 (5.93%)	4 / 136 (2.94%)
occurrences all number	11	4
Dizziness
subjects affected / exposed	17 / 135 (12.59%)	12 / 136 (8.82%)
occurrences all number	24	12
Dysgeusia
subjects affected / exposed	16 / 135 (11.85%)	15 / 136 (11.03%)
occurrences all number	23	16
Headache
subjects affected / exposed	9 / 135 (6.67%)	16 / 136 (11.76%)
occurrences all number	11	17
Neuropathy peripheral
subjects affected / exposed	48 / 135 (35.56%)	39 / 136 (28.68%)
occurrences all number	69	46
Paraesthesia
subjects affected / exposed	14 / 135 (10.37%)	18 / 136 (13.24%)
occurrences all number	19	24
Peripheral sensory neuropathy
subjects affected / exposed	30 / 135 (22.22%)	27 / 136 (19.85%)
occurrences all number	35	31
Polyneuropathy
subjects affected / exposed	8 / 135 (5.93%)	9 / 136 (6.62%)
occurrences all number	10	9
Blood and lymphatic system disorders
Thrombocytopenia
subjects affected / exposed	25 / 135 (18.52%)	21 / 136 (15.44%)
occurrences all number	39	33
Neutropenia
subjects affected / exposed	41 / 135 (30.37%)	37 / 136 (27.21%)
occurrences all number	85	62
Leukopenia
subjects affected / exposed	7 / 135 (5.19%)	5 / 136 (3.68%)
occurrences all number	15	5
Anaemia
subjects affected / exposed	32 / 135 (23.70%)	41 / 136 (30.15%)
occurrences all number	46	54
Gastrointestinal disorders
Dry mouth
subjects affected / exposed	9 / 135 (6.67%)	12 / 136 (8.82%)
occurrences all number	9	13
Constipation
subjects affected / exposed	34 / 135 (25.19%)	40 / 136 (29.41%)
occurrences all number	46	51
Abdominal pain upper
subjects affected / exposed	12 / 135 (8.89%)	16 / 136 (11.76%)
occurrences all number	13	16
Abdominal pain
subjects affected / exposed	28 / 135 (20.74%)	28 / 136 (20.59%)
occurrences all number	40	33
Abdominal distension
subjects affected / exposed	7 / 135 (5.19%)	5 / 136 (3.68%)
occurrences all number	8	5
Diarrhoea
subjects affected / exposed	60 / 135 (44.44%)	56 / 136 (41.18%)
occurrences all number	122	119
Vomiting
subjects affected / exposed	49 / 135 (36.30%)	49 / 136 (36.03%)
occurrences all number	72	77
Stomatitis
subjects affected / exposed	19 / 135 (14.07%)	16 / 136 (11.76%)
occurrences all number	25	29
Nausea
subjects affected / exposed	79 / 135 (58.52%)	70 / 136 (51.47%)
occurrences all number	132	126
Dysphagia
subjects affected / exposed	15 / 135 (11.11%)	22 / 136 (16.18%)
occurrences all number	19	23
Dyspepsia
subjects affected / exposed	7 / 135 (5.19%)	7 / 136 (5.15%)
occurrences all number	7	8
Gastrooesophageal reflux disease
subjects affected / exposed	9 / 135 (6.67%)	8 / 136 (5.88%)
occurrences all number	9	10
Skin and subcutaneous tissue disorders
Rash maculo-papular
subjects affected / exposed	1 / 135 (0.74%)	11 / 136 (8.09%)
occurrences all number	1	14
Alopecia
subjects affected / exposed	10 / 135 (7.41%)	9 / 136 (6.62%)
occurrences all number	10	9
Dry skin
subjects affected / exposed	11 / 135 (8.15%)	6 / 136 (4.41%)
occurrences all number	11	6
Palmar-plantar erythrodysaesthesia syndrome
subjects affected / exposed	18 / 135 (13.33%)	12 / 136 (8.82%)
occurrences all number	24	17
Pruritus
subjects affected / exposed	10 / 135 (7.41%)	14 / 136 (10.29%)
occurrences all number	12	15
Rash
subjects affected / exposed	24 / 135 (17.78%)	26 / 136 (19.12%)
occurrences all number	34	33
Endocrine disorders
Hyperthyroidism
subjects affected / exposed	3 / 135 (2.22%)	10 / 136 (7.35%)
occurrences all number	3	10
Hypothyroidism
subjects affected / exposed	18 / 135 (13.33%)	21 / 136 (15.44%)
occurrences all number	19	21
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	15 / 135 (11.11%)	18 / 136 (13.24%)
occurrences all number	15	19
Back pain
subjects affected / exposed	15 / 135 (11.11%)	16 / 136 (11.76%)
occurrences all number	17	19
Muscular weakness
subjects affected / exposed	9 / 135 (6.67%)	3 / 136 (2.21%)
occurrences all number	9	3
Pain in extremity
subjects affected / exposed	9 / 135 (6.67%)	5 / 136 (3.68%)
occurrences all number	10	5
Infections and infestations
Oral candidiasis
subjects affected / exposed	12 / 135 (8.89%)	6 / 136 (4.41%)
occurrences all number	13	7
Pneumonia
subjects affected / exposed	3 / 135 (2.22%)	7 / 136 (5.15%)
occurrences all number	3	7
Upper respiratory tract infection
subjects affected / exposed	5 / 135 (3.70%)	10 / 136 (7.35%)
occurrences all number	6	10
Urinary tract infection
subjects affected / exposed	11 / 135 (8.15%)	13 / 136 (9.56%)
occurrences all number	13	14
Metabolism and nutrition disorders
Decreased appetite
subjects affected / exposed	46 / 135 (34.07%)	48 / 136 (35.29%)
occurrences all number	53	56
Hyperglycaemia
subjects affected / exposed	8 / 135 (5.93%)	9 / 136 (6.62%)
occurrences all number	8	15
Hypocalcaemia
subjects affected / exposed	3 / 135 (2.22%)	10 / 136 (7.35%)
occurrences all number	4	12
Hypokalaemia
subjects affected / exposed	13 / 135 (9.63%)	17 / 136 (12.50%)
occurrences all number	21	21
Hypomagnesaemia
subjects affected / exposed	7 / 135 (5.19%)	6 / 136 (4.41%)
occurrences all number	12	7

More information

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Were there any global substantial amendments to the protocol? Yes

29 Jun 2018

Additional exclusion criterion added

16 Nov 2018

Revised text reflecting addition of Data Monitoring Committee

24 Jun 2019

Revised to update with current program requirements, updated company standards, and to provide additional clarifications throughout

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Clinical Trial Results:
A Randomized, Open-label, Phase II Clinical Trial of Relatlimab (anti-LAG-3) and Nivolumab in Combination with Chemotherapy Versus Nivolumab in Combination with Chemotherapy as First- Line Treatment in Patients with Gastric or Gastroesophageal Junction Adenocarcinoma

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: BICR-Assessed Objective Response Rate (ORR) in Randomized LAG-3 Positive (>=1 %) Participants

Primary: BICR-Assessed Objective Response Rate (ORR) in Randomized LAG-3 Positive (>=1 %) Participants

Primary: BICR-Assessed Objective Response Rate (ORR) in Randomized LAG-3 Positive (>=1 %) Participants - Extended Collection

Primary: BICR-Assessed Objective Response Rate (ORR) in Randomized LAG-3 Positive (>=1 %) Participants - Extended Collection

Secondary: Objective Response Rate (ORR)

Secondary: Objective Response Rate (ORR)

Secondary: Duration of Response (DOR)

Secondary: Duration of Response (DOR)

Secondary: Overall Survival (OS)

Secondary: Overall Survival (OS)

Secondary: Progression-Free Survival (PFS)

Secondary: Progression-Free Survival (PFS)

Secondary: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)

Secondary: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)

Secondary: Number of Participants who Died

Secondary: Number of Participants who Died

Secondary: Number of Participants with Laboratory Abnormalities in Specific Liver Tests

Secondary: Number of Participants with Laboratory Abnormalities in Specific Liver Tests

Secondary: Number of Participants with Laboratory Abnormalities in Specific Thyroid Tests

Secondary: Number of Participants with Laboratory Abnormalities in Specific Thyroid Tests

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

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Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials

Clinical Trial Results: A Randomized, Open-label, Phase II Clinical Trial of Relatlimab (anti-LAG-3) and Nivolumab in Combination with Chemotherapy Versus Nivolumab in Combination with Chemotherapy as First- Line Treatment in Patients with Gastric or Gastroesophageal Junction Adenocarcinoma

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: BICR-Assessed Objective Response Rate (ORR) in Randomized LAG-3 Positive (>=1 %) Participants

Primary: BICR-Assessed Objective Response Rate (ORR) in Randomized LAG-3 Positive (>=1 %) Participants

Primary: BICR-Assessed Objective Response Rate (ORR) in Randomized LAG-3 Positive (>=1 %) Participants - Extended Collection

Primary: BICR-Assessed Objective Response Rate (ORR) in Randomized LAG-3 Positive (>=1 %) Participants - Extended Collection

Secondary: Objective Response Rate (ORR)

Secondary: Objective Response Rate (ORR)

Secondary: Duration of Response (DOR)

Secondary: Duration of Response (DOR)

Secondary: Overall Survival (OS)

Secondary: Overall Survival (OS)

Secondary: Progression-Free Survival (PFS)

Secondary: Progression-Free Survival (PFS)

Secondary: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)

Secondary: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)

Secondary: Number of Participants who Died

Secondary: Number of Participants who Died

Secondary: Number of Participants with Laboratory Abnormalities in Specific Liver Tests

Secondary: Number of Participants with Laboratory Abnormalities in Specific Liver Tests

Secondary: Number of Participants with Laboratory Abnormalities in Specific Thyroid Tests

Secondary: Number of Participants with Laboratory Abnormalities in Specific Thyroid Tests

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A Randomized, Open-label, Phase II Clinical Trial of Relatlimab (anti-LAG-3) and Nivolumab in Combination with Chemotherapy Versus Nivolumab in Combination with Chemotherapy as First- Line Treatment in Patients with Gastric or Gastroesophageal Junction Adenocarcinoma