A Study of Nivolumab-relatlimab Fixed-dose Combination Versus Regorafenib or TAS-102 in Participants With Later-lines of Metastatic Colorectal Cancer

Study Overview
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Brief Summary
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The purpose of this study is to evaluate relatlimab in combination with nivolumab, administered as a fixed-dose combination (nivolumab-relatlimab FDC, also referred to as BMS-986213) for the treatment of non-microsatellite instability high (MSI-H)/deficient mismatch repair (dMMR) metastatic colorectal cancer (mCRC) participants who failed at least 1 but no more than 4 prior lines of therapy for metastatic disease.

Official Title
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A Phase 3, Randomized, Open-label Study of Relatlimab-nivolumab Fixed-dose Combination Versus Regorafenib or Trifluridine + Tipiracil (TAS-102) for Participants With Later-lines of Metastatic Colorectal Cancer

Conditions
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Colorectal Neoplasms

Intervention / Treatment
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* Drug: Nivolumab-relatlimab FDC
* Drug: Regorafenib
* Drug: TAS-102


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histological confirmed previously treated colorectal cancer with adenocarcinoma histology with metastatic or recurrent unresectable disease at study entry Participants must have: progressed during or within approximately 3 months following the last administration of approved standard therapies (at least 1, but not more than 4 prior lines of therapies in the metastatic setting), which must include a fluoropyrimidine, oxaliplatin, irinotecan, an anti-VEGF therapy, and anti-EGFR therapy (if RAS wild-type), if available in the respective country, or; been intolerant to prior systemic chemotherapy regimens if there is documented evidence of clinically significant intolerance despite adequate supportive measures Must have sufficient tumor tissue & evaluable PD-L1 expression to meet the study requirements Must have measurable disease per RECIST v1.1. Participants with lesions in a previously irradiated field as the sole site of measurable disease will be permitted to enroll provided the lesion(s) have demonstrated clear progression and can be measured accurately Exclusion Criteria: Prior treatment with either an immunotherapy or with regorafenib or with TAS-102 Untreated central nervous system (CNS) metastases, participants are eligible if CNS metastases have been treated and participants have neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) History of refractory hypertension not controlled with anti-hypertensive therapy, myocarditis (regardless of etiology), uncontrolled arrhythmias, acute coronary syndrome within 6 months prior to dosing, Class II congestive heart failure (as per the New York Heart Association Functional Classification), interstitial lung disease/pneumonitis or an active, known or suspected autoimmune disease Confirmed tumor microsatellite instable high/deficient mismatch repair (MSI-H/dMMR) status as per local standard testing; MSI/MMR test results from initial diagnosis are acceptable. 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 |
| --- | --- |
| Experimental: Arm A: Nivolumab + Relatlimab Fixed-dose Combination (FDC)<br> | Drug: Nivolumab-relatlimab FDC<br>* Specified dose on specified days<br>* Other names: BMS-986213;|
| Active Comparator: Arm B: Investigator's Choice<br>Treatment with Regorafenib or TAS-102 | Drug: Regorafenib<br>* Specified dose on specified days<br>* Other names: Stivarga;Drug: TAS-102<br>* Specified dose on specified days<br>* Other names: Lonsurf;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival (OS) in randomized participants with programmed death-ligand 1 (PD-L1) combined positive score (CPS) ≥ 1 |  | Up to 5 years after last participant randomized | 
| OS in all randomized participants |  | Up to 5 years after last participant randomized | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate (ORR) by Blinded Independent Central Review (BICR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 in randomized participants with PD-L1 CPS ≥ 1 |  | Up to 5 years after last participant randomized | 
| ORR by BICR per RECIST v1.1 in all randomized participants |  | Up to 5 years after last participant randomized | 
| Progression-free survival (PFS) by BICR per RECIST v1.1 in randomized participants with PD-L1 CPS ≥ 1 |  | Up to 5 years after last participant randomized | 
| PFS by BICR per RECIST v1.1 in all randomized participants |  | Up to 5 years after last participant randomized | 
| Duration of response (DoR) by BICR per RECIST v1.1 in responders with PD-L1 CPS ≥ 1 |  | Up to 5 years after last participant randomized | 
| DoR by BICR per RECIST v1.1 in all responders |  | Up to 5 years after last participant randomized | 
| Number of participants with adverse events (AEs) |  | Up to 135 days after participant's last dose | 
| Number of participants with serious adverse events (SAEs) |  | Up to 135 days after participant's last dose | 
| Number of participants with immune-mediated adverse events (IMAEs) |  | Up to 135 days after participant's last dose | 
| Number of participants with AEs leading to discontinuation |  | Up to 135 day's after participant's last dose | 
| Number of participants with clinical laboratory abnormalities |  | Up to 135 days after participant's last dose | 
| Time Until Definitive Deterioration-Physical Function (TUDD-PF): The time from randomization until definitive deterioration in the EORTC QLQ-C30 physical function scale score in randomized participants with PD-L1 CPS ≥ 1 | The EORTC (European Organisation for Research and Treatment of Cancer) Quality of Life Questionnaire-Core 30 (QLQ-C30) consists of 30 questions incorporated into 5 functional scales (physical, role, cognitive, emotional, and social functioning), 3 multi-item symptom scales (fatigue, pain, nausea and vomiting), a global health status / Quality of Life scale, and six single symptom items. All of the scale and single-item measures range in score from 0 to 100, where a higher score represents a higher response level. High functional scores indicates more favorable outcomes and a higher score on the symptom domains indicates higher symptom burden/less favorable patient outcome. | Up to follow up visit 2 (approximately 135 days after last dose) | 
| TUDD-PF: The time from randomization until definitive deterioration in the EORTC QLQ-C30 physical function scale score in all randomized participants |  | Up to follow up visit 2 (approximately 135 days after last dose) | 
| TUDD-QoL: The time from randomization until definitive deterioration in the EORTC QLQ-C30 global health status/QoL scale score in randomized participants with PD-L1 CPS ≥ 1 | QoL = Quality of Life. The EORTC (European Organisation for Research and Treatment of Cancer) Quality of Life Questionnaire-Core 30 (QLQ-C30) consists of 30 questions incorporated into 5 functional scales (physical, role, cognitive, emotional, and social functioning), 3 multi-item symptom scales (fatigue, pain, nausea and vomiting), a global health status / Quality of Life scale, and six single symptom items. All of the scale and single-item measures range in score from 0 to 100, where a higher score represents a higher response level. High functional scores indicates more favorable outcomes and a higher score on the symptom domains indicates higher symptom burden/less favorable patient outcome. | Up to follow up visit 2 (approximately 135 days after last dose) | 
| TUDD-QoL: The time from randomization until definitive deterioration in the EORTC QLQ-C30 global health status/QoL scale score in all randomized participants |  | Up to follow up visit 2 (approximately 135 days after last dose) | 
| PFS by investigator per RECIST v1.1 in randomized participants with PD-L1 CPS ≥ 1 |  | Up to 5 years after last participant randomized | 
| PFS by investigator per RECIST v1.1 in all randomized participants |  | Up to 5 years after last participant randomized | 
| ORR by investigator per RECIST v1.1 in randomized participants with PD-L1 CPS ≥ 1 |  | Up to 5 years after last participant randomized | 
| ORR by investigator per RECIST v1.1 in all randomized participants |  | Up to 5 years after last participant randomized | 
| DoR by investigator per RECIST v1.1 in responders with PD-L1 CPS ≥ 1 |  | Up to 5 years after last participant randomized | 
| DoR by investigator per RECIST v1.1 in all randomized participants |  | Up to 5 years after last participant randomized | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Micro-satellite Stable (MSS) Metastatic Colorectal Cancer (mCRC), Relatlimab, Nivolumab, BMS-986213, Regorafenib, Stivarga, Lonsurf