A Study of Nivolumab and Relatlimab in Combination With Bevacizumab in Advanced Liver Cancer

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and effectiveness of triplet therapy of nivolumab, relatlimab and bevacizumab versus nivolumab and bevacizumab in participants with untreated advanced/metastatic hepatocellular carcinoma (HCC).

Official Title
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A Phase 1/2, Safety Confirmation, Placebo-controlled, Randomized Study of Nivolumab in Combination With Relatlimab and Bevacizumab in Treatment-naive Advanced/Metastatic Hepatocellular Carcinoma

Conditions
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Carcinoma, Hepatocellular

Intervention / Treatment
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* Drug: Relatlimab
* Drug: Nivolumab
* Drug: Bevacizumab
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed advanced/metastatic hepatocellular carcinoma (HCC) Naïve to systemic therapy for advanced/metastatic HCC (prior neo-adjuvant or adjuvant immunotherapy is permitted if recurrence occurs ≥ 6 months after treatment completion and the case is discussed with BMS medical team) Child-Pugh score of 5 or 6 (ie, Child-Pugh A) Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 Exclusion Criteria: Known fibrolamellar HCC, sarcomatoid HCC or mixed cholangiocarcinoma and HCC Prior allogenic stem cell or solid organ transplantation Untreated symptomatic central nervous system (CNS) metastases Clinically significant ascites as defined by: i) Prior ascites that required treatment and requires on-going prophylaxis, or ii) Current ascites requiring treatment 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A: Relatlimab + Nivolumab + Bevacizumab<br> | Drug: Relatlimab<br>* Specified dose on specified days<br>* Other names: BMS-986016;Drug: Nivolumab<br>* Specified dose on specified days<br>* Other names: Opdivo;Drug: Bevacizumab<br>* Specified dose on specified days<br>* Other names: Avastin;|
| Experimental: Arm B: Placebo + Nivolumab + Bevacizumab<br> | Drug: Nivolumab<br>* Specified dose on specified days<br>* Other names: Opdivo;Drug: Bevacizumab<br>* Specified dose on specified days<br>* Other names: Avastin;Other: Placebo<br>* Specified dose on specified days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of dose-limiting toxicities (DLTs) |  | Up to 6 weeks | 
| Overall Response Rate (ORR) by Blinded Independent Central Review (BICR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 |  | Assessed up to 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) by BICR per RECIST v1.1 in all randomized participants that are lymphocyte activation gene 3 (LAG-3) positive |  | Assessed up to 3 years | 
| PFS by BICR per RECIST v1.1 in all randomized participants |  | Assessed up to 3 years | 
| ORR by BICR per RECIST v1.1 in all randomized participants that are LAG-3 positive |  | Assessed up to 3 years | 
| Overall Survival (OS) of all randomized participants |  | Assessed up to 3 years | 
| OS of all randomized participants that are LAG-3 positive |  | Assessed up to 3 years | 
| Number of participants with adverse events (AEs) |  | Up to 135 days after participant's last dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HCC, Hepatocellular Carcinoma, Liver Cancer, Relatlimab, Nivolumab, Bevacizumab, First line HCC