A Study to Test Combination Treatments in Participants With Advanced Gastric Cancer

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the preliminary efficacy, safety, and tolerability of Nivolumab in combination with Ipilimumab or other treatment therapies in participants with advanced gastric cancer.

Official Title
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A Phase 2, Fast Real-time Assessment of Combination Therapies in Immuno-ONcology Study in Participants With Advanced Gastric Cancer (FRACTION-Gastric Cancer)

Conditions
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Advanced Gastric Cancer

Intervention / Treatment
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* Biological: Nivolumab
* Biological: Ipilimumab
* Biological: Relatlimab
* Biological: BMS-986205
* Drug: Rucaparib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Inoperable, advanced or metastatic esophageal cancer (EC), gastric cancer (GC) or gastroesophageal junction (GEJ) carcinoma and have histologically confirmed predominant adenocarcinoma and/or squamous carcinoma Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1 At least 1 lesion with measurable disease Exclusion Criteria: HER2-positive tumor and previously untreated with trastuzumab Suspected, known or progressive central nervous system metastases Other active malignancy requiring concurrent intervention Active, known or suspected autoimmune disease Other protocol-defined inclusion/exclusion criteria 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 |
| --- | --- |
| Active Comparator: Nivolumab + Ipilimumab<br> | Biological: Nivolumab<br>* Specified dose on specified days<br>* Other names: BMS-936558;Biological: Ipilimumab<br>* Specified dose on specified days<br>* Other names: BMS-734016;|
| Experimental: Nivolumab + Relatlimab<br> | Biological: Nivolumab<br>* Specified dose on specified days<br>* Other names: BMS-936558;Biological: Relatlimab<br>* Specified dose on specified days<br>* Other names: BMS-986016;|
| Experimental: Nivolumab + BMS-986205<br> | Biological: Nivolumab<br>* Specified dose on specified days<br>* Other names: BMS-936558;Biological: BMS-986205<br>* Specified dose on specified days<br>|
| Experimental: Nivolumab + Rucaparib<br> | Biological: Nivolumab<br>* Specified dose on specified days<br>* Other names: BMS-936558;Drug: Rucaparib<br>* Specified dose on specified days<br>* Other names: Rubraca;|
| Experimental: Ipilimumab + Rucaparib<br> | Biological: Ipilimumab<br>* Specified dose on specified days<br>* Other names: BMS-734016;Drug: Rucaparib<br>* Specified dose on specified days<br>* Other names: Rubraca;|
| Experimental: Nivolumab + Ipilimumab + Rucaparib<br> | Biological: Nivolumab<br>* Specified dose on specified days<br>* Other names: BMS-936558;Biological: Ipilimumab<br>* Specified dose on specified days<br>* Other names: BMS-734016;Drug: Rucaparib<br>* Specified dose on specified days<br>* Other names: Rubraca;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) by Investigator | ORR is the percent of participants whose best overall response (BOR) is complete response (CR) or partial response (PR). BOR is the best response from the start of the study treatment until objectively documented progression per RECIST v1.1 or subsequent anticancer therapy, whichever occurs first. CR is the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) have reduction in short axis to <10 mm. PR is at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. The Response Evaluation Criteria in Solid Tumors (RECIST) is a standard way to measure the response of a tumor to treatment. CR+PR, confidence interval based on Clopper and Pearson method. | From first dose of study treatment until progression or subsequent anticancer therapy, whichever occurs first (up to approximately 65 months) | 
| Median Duration of Response (DOR) | Duration of Response (DOR) is the time between the date of first response and the date of first documented disease progression as determined by RECIST 1.1 or death due to any cause, whichever occurred first. Complete Response (CR) is the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial Response (PR) is at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Median computed using Kaplan -Meier method. | From first dose to date of first documented tumor progression or death due to any cause, whichever occurred first (up to approximately 65 months) | 
| Kaplan-Meier Analysis of Progression Free Survival Rate (PFSR) at 24 Weeks | The PFSR at 24 weeks is defined as the proportion of treated participants remaining progression free and surviving at 24 weeks since the first dosing date. Progressive Disease (PD) is at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Point estimates are derived from Kaplan-Meier analyses, the 95% CIs are derived from Greenwood formula. | 24 weeks after first dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With AEs, SAEs, AEs Leading to Discontinuation, and Death | An Adverse Event (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. Serious Adverse Event (SAE) is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening (defined as an event in which the participant was at risk of death at the time of the event; it does not refer to an event which hypothetically might have caused death if it were more severe), requires inpatient hospitalization or causes prolongation of existing hospitalization. | From first dose to 100 days after last dose of study therapy (assessed up to approximately 30 months) | 
| Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests | The number of participants with laboratory abnormalities in specific thyroid tests based on US conventional units. TSH = Thyroid Stimulating Hormone LLN = Lower Limit of Normal ULN = Upper Limit of Normal. | From first dose to 100 days after last dose of study therapy (approximately 30 months) | 
| Number of Participants With Laboratory Abnormalities in Specific Liver Tests | The number of participants with laboratory abnormalities in specific liver tests based on US conventional units. ALT = Alanine Aminotransferase AST = Aspartate Aminotransferase ULN = Upper Limit of Normal | From first dose to 100 days after last dose of study therapy (approximately 30 months) |