An Investigational Immuno-therapy Study to Assess the Safety, Tolerability and Effectiveness of Anti-LAG-3 With and Without Anti-PD-1 in the Treatment of Solid Tumors

Study Overview
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Brief Summary
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The purpose of the study is to assess the safety, tolerability and effectiveness of experimental medication BMS-986016 administered alone and in combination with nivolumab in patients with solid tumors that have spread and/or cannot be removed by surgery. The following tumor types are included in this study: Non-Small Cell Lung Cancer (NSCLC), gastric cancer, hepatocellular carcinoma, renal cell carcinoma, bladder cancer, squamous cell carcinoma of the head and neck, and melanoma, that have NOT previously been treated with immunotherapy. NSCLC and melanoma that HAVE previously been treated with immunotherapy.

Official Title
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A Phase I/2a Dose Escalation and Cohort Expansion Study of the Safety, Tolerability, and Efficacy of Anti-LAG-3 Monoclonal Antibody (BMS-986016) Administered Alone and in Combination With Anti-PD-1 Monoclonal Antibody (Nivolumab, BMS-936558) in Advanced Solid Tumors

Conditions
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Neoplasms by Site

Intervention / Treatment
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* Biological: Relatlimab
* Biological: Nivolumab
* Biological: BMS-986213


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: For Dose escalation: subjects with cervical, ovarian, bladder and colorectal cancer (CRC), head and neck, gastric and hepatocellular cancer naive to immuno-oncology agents; 1st line melanoma and 1st line/2nd line NSCLC; Renal Cell Carcinoma naive to IO; NSCLC progressing while on or after therapy with anti-PD1/anti-PDL-1 and melanoma subjects progressed while-on or after treatment with anti-PD1 or anti-PDL1 with or without anti-CTLA-4. For Dose Expansion: all of the above in escalation except for cervical, ovarian, and CRC Progressed, or been intolerant to, at least one standard treatment regimen, except for participants in 1st line cohorts. ECOG performance status between 0 and 2 At least 1 lesion with measurable disease at baseline Availability of an existing tumor biopsy sample (and consent to allow pre-treatment tumor biopsy) Exclusion Criteria: Primary central nervous system (CNS) tumors or solid tumors with CNS metastases as the only site of active disease Autoimmune disease Encephalitis, meningitis, or uncontrolled seizures in the year prior to informed consent Uncontrolled CNS metastases Other protocol defined inclusion/exclusion criteria could apply

Ages Eligible for Study
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Minimum Age: 12 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: Relatlimab<br>Relatlimab (BMS-986016) specified dose on specified days | Biological: Relatlimab<br> <br> * Other names: Anti-LAG-3 (Anti-Lymphocyte Activation Gene-3);|
| Experimental: Relatlimab + Nivolumab<br>Relatlimab (BMS-986016) + Nivolumab (BMS-936558) specified dose on specified days | Biological: Relatlimab<br> <br> * Other names: Anti-LAG-3 (Anti-Lymphocyte Activation Gene-3);Biological: Nivolumab<br> <br> * Other names: BMS-936558;|
| Experimental: BMS-986213<br>Relatlimab (BMS-986016) + Nivolumab (BMS-936558) | Biological: BMS-986213<br>* Relatlimab + Nivolumab<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants with Adverse Events (AEs) | Grade 3 or higher per CTCAE v4 (Common Terminology Criteria for Adverse Events) | Approximately Up to 3 years | 
| Proportion of participants with Serious Adverse Events (SAEs) | Grade 3 or higher per CTCAE v4 ( Common Terminology Criteria for Adverse Events) | Approximately Up to 3 years | 
| Proportion of Deaths |  | Approximately Up to 3 years | 
| Proportion of participants with laboratory abnormalities in blood |  | Approximately Up to 3 years | 
| Proportion of participants with laboratory abnormalities in blood serum |  | Approximately Up to 3 years | 
| Proportion of participants with laboratory abnormalities in urine |  | Approximately Up to 3 years | 
| Objective response rate (ORR) |  | Approximately 3 years | 
| Disease control rate (DCR) |  | Approximately 3 years | 
| Duration of response (DOR) |  | Approximately 3 years | 
| Number of AEs in the Broad Scope MedDRA Anaphylactic Reaction SMQ |  | Approximately 3 years | 
| Proportion of participants with AEs leading to discontinuation of treatment |  | Approximately up to 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum observed serum concentration (Cmax) of BMS-986016 administered both alone and in combination with nivolumab |  | Approximately 2.3 years | 
| Time of maximum observed serum concentration (Tmax) of BMS-986016 administered both alone and in combination with nivolumab |  | Approximately 2.3 years | 
| Trough observed serum concentration (Ctrough) of BMS-986016 administered both alone and in combination with nivolumab |  | Approximately 2.3 years | 
| Concentration at the end of a dosing interval (Ctau) [Eg: concentration at 336 hours] of BMS-986016 administered both alone and in combination with nivolumab |  | Approximately 2.3 years | 
| Area under the concentration-time curve in one dosing interval [AUC(TAU)] of BMS-986016 administered both alone and in combination with nivolumab |  | Approximately 2.3 years | 
| Total body clearance (CLT) of BMS-986016 administered both alone and in combination with nivolumab |  | Approximately 2.3 years | 
| Volume of distribution at steady state (Vss) of BMS-986016 administered both alone and in combination with nivolumab |  | Approximately 2.3 years | 
| Effective elimination half-life that explains the degree of area under the concentration-time curve (AUC) accumulation observed (T-HALFeff AUC) of BMS-986016 administered both alone and in combination with nivolumab |  | Approximately 2.3 years | 
| Effective elimination half-life that explains the degree of Cmax accumulation observed (T-HALFeff Cmax) of BMS-986016 administered both alone and in combination with nivolumab |  | Approximately 2.3 years | 
| Accumulation index; ratio of AUC(TAU) at steady state to AUC(TAU) after the first dose (AI_AUC) of BMS-986016 administered both alone and in combination with nivolumab |  | Approximately 2.3 years | 
| Cmax accumulation index; ratio of Cmax at steady state to Cmax after the first dose (AI_Cmax) of BMS-986016 administered both alone and in combination with nivolumab |  | Approximately 2.3 years | 
| Ctau accumulation index; ratio of Ctau at steady state to Ctau after the first dose (AI_Ctau) of BMS-986016 administered both alone and in combination with nivolumab |  | Approximately 2.3 years | 
| Degree of fluctuation (DF) or fluctuation index ([Cmax - Ctau]/Css,avg]) of BMS-986016 administered both alone and in combination with nivolumab |  | Approximately 2.3 years | 
| Immunogenicity measured by anti-drug antibody (ADA) for BMS-986016 (all participants) and nivolumab |  | Approximately 2.3 years | 
| QTc interval from centrally read electrocardiograms (ECGs) |  | Approximately 2.3 years | 
| Best overall response (BOR) |  | Approximately 3 years | 
| ORR |  | Approximately 3 years | 
| DCR |  | Approximately 3 years | 
| Duration of response (DOR) |  | Approximately 3 years | 
| Progression-free survival (PFS) rates |  | Up to approximately 3 years | 
| Overall survival (OS) |  | Approximately 2 years | 
| Number of AEs in the Narrow Scope MedDRA Anaphylactic Reaction SMQ |  | Approximately 3 years |