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

Phase 1

Active, not recruiting

• Conditions: Neoplasms by Site
• Interventions: Biological: Relatlimab; Biological: BMS-986213; Biological: Nivolumab

• Registration Number: NCT01968109
• Lead Sponsor: Bristol-Myers Squibb

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2013-09-25
• Study First Submitted QC: 2013-10-18
• Study First Posted: 2013-10-23
• Study Start: 2013-11-05
• Primary Completion: 2024-05-22
• Status Verified: 2024-07
• Last Update Submitted: 2024-07-16
• Last Update Posted: 2024-07-17
• Study Completion: 2025-01-31

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 1499

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)

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Relatlimab	Relatlimab	Relatlimab (BMS-986016) specified dose on specified days
Relatlimab + Nivolumab	Relatlimab	Relatlimab (BMS-986016) + Nivolumab (BMS-936558) specified dose on specified days
Relatlimab + Nivolumab	Nivolumab	Relatlimab (BMS-986016) + Nivolumab (BMS-936558) specified dose on specified days
BMS-986213	BMS-986213	Relatlimab (BMS-986016) + Nivolumab (BMS-936558)

Primary Outcome Measures

Name	Time	Method
Proportion of participants with Adverse Events (AEs)	Approximately Up to 3 years	Grade 3 or higher per CTCAE v4 (Common Terminology Criteria for Adverse Events)
Proportion of participants with laboratory abnormalities in blood	Approximately Up to 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 Deaths	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
Proportion of participants with AEs leading to discontinuation of treatment	Approximately up to 3 years
Proportion of participants with Serious Adverse Events (SAEs)	Approximately Up to 3 years	Grade 3 or higher per CTCAE v4 ( Common Terminology Criteria for Adverse Events)
Disease control rate (DCR)	Approximately 3 years
Objective response rate (ORR)	Approximately 3 years

Secondary Outcome Measures

Name	Time	Method
Time of maximum observed serum concentration (Tmax) 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
Progression-free survival (PFS) rates	Up to approximately 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
Maximum observed serum concentration (Cmax) 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
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
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
QTc interval from centrally read electrocardiograms (ECGs)	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
Immunogenicity measured by anti-drug antibody (ADA) for BMS-986016 (all participants) and 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
DCR	Approximately 3 years
Duration of response (DOR)	Approximately 3 years
Overall survival (OS)	Approximately 2 years
Best overall response (BOR)	Approximately 3 years
Number of AEs in the Narrow Scope MedDRA Anaphylactic Reaction SMQ	Approximately 3 years
ORR	Approximately 3 years

Trial Locations

Locations (54)

Local Institution - 0010; 🇺🇸 Pittsburgh, Pennsylvania, United States

Local Institution - 0057; 🇺🇸 Dallas, Texas, United States

Local Institution - 0043; 🇺🇸 La Jolla, California, United States

Local Institution - 0053; 🇺🇸 Aurora, Colorado, United States

Local Institution - 0003; 🇺🇸 Chicago, Illinois, United States

Local Institution - 0058; 🇺🇸 Tampa, Florida, United States

Local Institution - 0048; 🇺🇸 Niles, Illinois, United States

Local Institution - 0001; 🇺🇸 Boston, Massachusetts, United States

Local Institution - 0004; 🇺🇸 Baltimore, Maryland, United States

Local Institution - 0011; 🇺🇸 Detroit, Michigan, United States

Local Institution - 0051; 🇺🇸 Rochester, Minnesota, United States

Local Institution - 0005; 🇺🇸 New York, New York, United States

Local Institution - 0044; 🇺🇸 Saint Louis, Missouri, United States

Local Institution - 0047; 🇺🇸 Allentown, Pennsylvania, United States

Local Institution - 0002; 🇺🇸 Portland, Oregon, United States

Local Institution - 0008; 🇺🇸 Seattle, Washington, United States

Local Institution - 0045; 🇺🇸 Houston, Texas, United States

Local Institution - 0029; 🇦🇺 North Sydney, New South Wales, Australia

Local Institution - 0031; 🇦🇺 Brisbane, Queensland, Australia

Local Institution - 0039; 🇦🇺 Southport, Queensland, Australia

Local Institution - 0033; 🇦🇺 Melbourne, Victoria, Australia

Local Institution - 0023; 🇦🇹 Wien, Austria

Local Institution - 0050; 🇨🇦 Quebec City, Quebec, Canada

Local Institution - 0024; 🇦🇹 Wien, Austria

Local Institution - 0049; 🇨🇦 Toronto, Ontario, Canada

Local Institution - 0021; 🇫🇮 Helsinki, Uusimaa, Finland

Local Institution - 0038; 🇫🇷 Marseille Cedex 5, France

Local Institution - 0037; 🇫🇷 Nantes Cedex 01, France

Local Institution - 0036; 🇫🇷 Pierre Benite Cedex, France

Local Institution - 0026; 🇫🇷 Toulouse Cedex 9, France

Local Institution - 0018; 🇫🇷 Villejuif, France

Local Institution - 0007; 🇩🇪 Essen, Germany

Local Institution - 0040; 🇩🇪 Heilbronn, Germany

Local Institution - 0014; 🇮🇹 Milano, Italy

Local Institution - 0041; 🇩🇪 Wuerzburg, Germany

Local Institution - 0013; 🇮🇹 Napoli, Italy

Local Institution - 0035; 🇮🇹 Padova, Italy

Local Institution - 0054; 🇯🇵 Sunto-gun, Shizuoka, Japan

Local Institution - 0052; 🇯🇵 Chuo-ku, Tokyo, Japan

Local Institution - 0055; 🇯🇵 Nagoya-shi, Aichi, Japan

Local Institution - 0059; 🇯🇵 Sapporo-shi, Hokkaido, Japan

Local Institution - 0025; 🇳🇱 Amsterdam, Netherlands

Local Institution - 0019; 🇳🇴 Oslo, Norway

Local Institution - 0046; 🇪🇸 Malaga, Spain

Local Institution - 0015; 🇪🇸 Barcelona, Spain

Local Institution - 0017; 🇨🇭 Lausanne, Switzerland

Local Institution - 0006; 🇪🇸 Pamplona, Spain

Local Institution - 0027; 🇬🇧 London, Greater London, United Kingdom

Local Institution - 0016; 🇨🇭 Zuerich, Switzerland

Local Institution - 0034; 🇬🇧 Manchester, United Kingdom

Local Institution - 0032; 🇦🇺 Nedlands, Western Australia, Australia

Local Institution - 0028; 🇩🇰 Copenhagen, Denmark

Local Institution - 0020; 🇩🇰 Herlev, Denmark

Local Institution - 0022; 🇬🇧 London, Greater London, United Kingdom