Gastric Cancer,Gastroesophageal Junction Cancer

The main purpose of this study is to compare how long patients with gastric or gastroesophageal junction cancer live after receiving nivolumab and ipilimumab or nivolumab and chemotherapy compared with patients receiving chemotherapy alone.

Nivolumab/Ipilimumab/Oxaliplatin/Fluorouracil/Leucovorin/Capecitabine

Nivolumab

Solution for Injection

10mg/mL, 10mL/vial

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

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


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

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

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

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

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

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

Inclusion Criteria:

Male or Female at least 18 years of age
Must have gastric cancer or gastroesophageal junction cancer that cannot be operated on and that is advanced or has spread out
Did not receive neoadjuvant or adjuvant treatment (chemotherapy, radiotherapy, or both) for their disease within the last 6 months
Must have full activity or, if limited, must be able to walk and carry out light activities such as light house work or office work
Must agree to provide tumor tissue sample, either from a previous surgery or biopsy within 6 months or fresh, prior to the start of treatment in this study

Exclusion Criteria:

Presence of tumor cells in the brain or spinal cord that have not been treated
Active known or suspected autoimmune disease
Any serious or uncontrolled medical disorder or active infection
Known history of positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
Any positive test result for hepatitis B or C indicating acute or chronic infection
Other protocol-defined inclusion/exclusion criteria apply