An Investigational Study of Immunotherapy Combinations With Chemotherapy in Patients With Gastric or Gastroesophageal Junction (GEJ) Cancers

Study Overview
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Brief Summary
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The purpose of this study is to determine the efficacy and safety of investigational drug relatlimab plus nivolumab in combination with chemotherapy in participants with unresectable, untreated, locally advanced or metastatic gastric or GEJ cancer.

Official Title
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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

Conditions
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Gastric Cancer, Cancer of the Stomach, Esophagogastric Junction

Intervention / Treatment
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* Biological: BMS-986213
* Biological: Nivolumab
* Drug: XELOX
* Drug: FOLFOX
* Drug: SOX


Participation Criteria
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Eligibility Criteria
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For more information regarding Bristol-Myers Squibb Clinical Trial participation, please visit www.BMSStudyConnect.com Inclusion Criteria: Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1 Histologically- or cytologically-confirmed diagnosis of unresectable and either locally advanced, or metastatic gastric cancer or GEJ adenocarcinoma No prior treatment with systemic treatment (including HER 2 inhibitors) given as primary therapy for unresectable and either locally advanced, or metastatic GC or GEJ adenocarcinoma Tumor tissue must be provided for biomarker analyses Exclusion Criteria: Participants with HER2 positive status Participants with known untreated central nervous system (CNS) metastases Uncontrolled or significant cardiovascular disease Other protocol defined inclusion/exclusion criteria could apply

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BMS-986213 + investigator's choice chemotherapy<br>BMS-986213 + XELOX or BMS-986213 + FOLFOX or BMS-986213 + SOX | Biological: BMS-986213<br>* Relatlimab + Nivolumab specified dose on specified days<br>Biological: Nivolumab<br>* Specified dose on specified days<br>* Other names: BMS-936558;Drug: XELOX<br>* Oxaliplatin + capecitabine<br>Drug: FOLFOX<br>* Oxaliplatin + leucovorin + fluorouracil<br>Drug: SOX<br>* Oxaliplatin + tegafur/gimeracil/oteracil potassium<br>|
| Experimental: Nivolumab + investigator's choice chemotherapy<br>Nivolumab + XELOX or Nivolumab + FOLFOX or Nivolumab + SOX | Biological: Nivolumab<br>* Specified dose on specified days<br>* Other names: BMS-936558;Drug: XELOX<br>* Oxaliplatin + capecitabine<br>Drug: FOLFOX<br>* Oxaliplatin + leucovorin + fluorouracil<br>Drug: SOX<br>* Oxaliplatin + tegafur/gimeracil/oteracil potassium<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| BICR-Assessed Objective Response Rate (ORR) in Randomized LAG-3 Positive (>=1 %) Participants | 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 | Up to 25 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) | 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. | Up to 25 months | 
| Duration of Response (DOR) | Duration of Response (DOR) based on Blinded Independent Central Review (BICR) and investigator is defined as the time between the date of first documented response (complete response or partial response) 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. | Up to 25 months | 
| Overall Survival (OS) | 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. | Up to 25 months | 
| Progression-Free Survival (PFS) | 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. | Up to 25 months | 
| Number of Participants With Adverse Events (AEs) | 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) to assess the overall safety and tolerability of BMS-986213 in combination with chemotherapy vs. Nivolumab in combination with chemotherapy. | From first dose to 30 days post last dose (Up to 23 months) | 
| Number of Deaths | Number of deaths in each arm to assess the overall safety and tolerability of BMS-986213 in combination with chemotherapy vs. Nivolumab in combination with chemotherapy. | Up to 25 months | 
| Number of Participants With Laboratory Abnormalities in Specific Liver Tests | Number of participants with laboratory abnormalities in specific liver tests based on US conventional units to assess the overall safety and tolerability of BMS-986213 in combination with chemotherapy vs. Nivolumab in combination with chemotherapy. 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 | From first dose to up to 30 days post last dose (Up to 23 months) | 
| Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests | 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 | From first dose to up to 30 days post last dose (Up to 23 months) |