Efficacy Study of Nivolumab Plus Ipilimumab or Nivolumab Plus Chemotherapy Against Chemotherapy in Stomach Cancer or Stomach/Esophagus Junction Cancer (CheckMate649)
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ClinicalTrials.gov Identifier: NCT02872116 |
Recruitment Status :
Active, not recruiting
First Posted : August 19, 2016
Results First Posted : June 28, 2022
Last Update Posted : May 6, 2023
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Condition or disease | Intervention/treatment | Phase |
---|---|---|
Gastric Cancer Gastroesophageal Junction Cancer Esophageal Adenocarcinoma | Drug: Nivolumab Drug: Ipilimumab Drug: Oxaliplatin Drug: Capecitabine Drug: Leucovorin Drug: Fluorouracil | Phase 3 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 2031 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | A Randomized, Multicenter, Open-Label, Phase 3 Study of Nivolumab Plus Ipilimumab or Nivolumab in Combination With Oxaliplatin Plus Fluoropyrimidine Versus Oxaliplatin Plus Fluoropyrimidine in Subjects With Previously Untreated Advanced or Metastatic Gastric or Gastroesophageal Junction Cancer |
Actual Study Start Date : | October 12, 2016 |
Actual Primary Completion Date : | May 27, 2020 |
Estimated Study Completion Date : | May 31, 2024 |

Arm | Intervention/treatment |
---|---|
Experimental: Nivolumab + Ipilimumab
Nivolumab + Ipilimumab for 4 doses, followed by Nivolumab monotherapy Enrollment is closed for this arm |
Drug: Nivolumab
Specified dose on specified days
Other Names:
Drug: Ipilimumab Specified dose on specified days
Other Names:
|
Active Comparator: XELOX (Oxaliplatin + Capecitabine) |
Drug: Oxaliplatin
Specified dose on specified days Drug: Capecitabine Specified dose on specified days |
Active Comparator: FOLFOX (Oxaliplatin + Leucovorin + Fluorouracil) |
Drug: Oxaliplatin
Specified dose on specified days Drug: Leucovorin Specified dose on specified days Drug: Fluorouracil Specified dose on specified days |
Experimental: Nivolumab + XELOX |
Drug: Nivolumab
Specified dose on specified days
Other Names:
Drug: Oxaliplatin Specified dose on specified days Drug: Capecitabine Specified dose on specified days |
Experimental: Nivolumab + FOLFOX |
Drug: Nivolumab
Specified dose on specified days
Other Names:
Drug: Oxaliplatin Specified dose on specified days Drug: Leucovorin Specified dose on specified days Drug: Fluorouracil Specified dose on specified days |
- 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.
- 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.

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Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
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

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02872116

Study Director: | Bristol-Myers Squibb | Bristol-Myers Squibb |
Documents provided by Bristol-Myers Squibb:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: | Bristol-Myers Squibb |
ClinicalTrials.gov Identifier: | NCT02872116 |
Other Study ID Numbers: |
CA209-649 2016-001018-76 ( EudraCT Number ) |
First Posted: | August 19, 2016 Key Record Dates |
Results First Posted: | June 28, 2022 |
Last Update Posted: | May 6, 2023 |
Last Verified: | May 2023 |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
Adenocarcinoma Carcinoma Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Neoplasms Leucovorin Fluorouracil Capecitabine Oxaliplatin Nivolumab Ipilimumab Antimetabolites Molecular Mechanisms of Pharmacological Action |
Antimetabolites, Antineoplastic Antineoplastic Agents Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Antineoplastic Agents, Immunological Immune Checkpoint Inhibitors Antidotes Protective Agents Vitamin B Complex Vitamins Micronutrients |