Description:
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.
Title
- Brief Title: 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
- Official Title: 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
Clinical Trial IDs
- ORG STUDY ID:
CA224-020
- SECONDARY ID:
2014-002605-38
- NCT ID:
NCT01968109
Conditions
Interventions
| Drug | Synonyms | Arms |
|---|
| Relatlimab | BMS-986016, Anti-LAG-3 (Anti-Lymphocyte Activation Gene-3) | Relatlimab |
| Nivolumab | Anti-PD-1 (Anti-Programmed-Death-1), BMS-936558 | Relatlimab + Nivolumab |
| BMS-986213 | | BMS-986213 |
Purpose
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.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Relatlimab | Experimental | Relatlimab (BMS-986016) specified dose on specified days | |
| Relatlimab + Nivolumab | Experimental | Relatlimab (BMS-986016) + Nivolumab (BMS-936558) specified dose on specified days | |
| BMS-986213 | Experimental | Relatlimab (BMS-986016) + Nivolumab (BMS-936558) | |
Eligibility Criteria
For more information regarding BMS clinical trial participation, please visit
www.BMSStudyConnect.com.
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
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 12 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Proportion of participants with Adverse Events (AEs) |
| Time Frame: | Approximately Up to 3 years |
| Safety Issue: | |
| Description: | Grade 3 or higher per CTCAE v4 (Common Terminology Criteria for Adverse Events) |
Secondary Outcome Measures
| Measure: | Maximum observed serum concentration (Cmax) of BMS-986016 administered both alone and in combination with nivolumab |
| Time Frame: | Approximately 2.3 years |
| Safety Issue: | |
| Description: | |
| Measure: | Time of maximum observed serum concentration (Tmax) of BMS-986016 administered both alone and in combination with nivolumab |
| Time Frame: | Approximately 2.3 years |
| Safety Issue: | |
| Description: | |
| Measure: | Trough observed serum concentration (Ctrough) of BMS-986016 administered both alone and in combination with nivolumab |
| Time Frame: | Approximately 2.3 years |
| Safety Issue: | |
| Description: | |
| Measure: | 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 |
| Time Frame: | Approximately 2.3 years |
| Safety Issue: | |
| Description: | |
| Measure: | Area under the concentration-time curve in one dosing interval [AUC(TAU)] of BMS-986016 administered both alone and in combination with nivolumab |
| Time Frame: | Approximately 2.3 years |
| Safety Issue: | |
| Description: | |
| Measure: | Total body clearance (CLT) of BMS-986016 administered both alone and in combination with nivolumab |
| Time Frame: | Approximately 2.3 years |
| Safety Issue: | |
| Description: | |
| Measure: | Volume of distribution at steady state (Vss) of BMS-986016 administered both alone and in combination with nivolumab |
| Time Frame: | Approximately 2.3 years |
| Safety Issue: | |
| Description: | |
| Measure: | 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 |
| Time Frame: | Approximately 2.3 years |
| Safety Issue: | |
| Description: | |
| Measure: | 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 |
| Time Frame: | Approximately 2.3 years |
| Safety Issue: | |
| Description: | |
| Measure: | 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 |
| Time Frame: | Approximately 2.3 years |
| Safety Issue: | |
| Description: | |
| Measure: | 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 |
| Time Frame: | Approximately 2.3 years |
| Safety Issue: | |
| Description: | |
| Measure: | 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 |
| Time Frame: | Approximately 2.3 years |
| Safety Issue: | |
| Description: | |
| Measure: | Degree of fluctuation (DF) or fluctuation index ([Cmax - Ctau]/Css,avg]) of BMS-986016 administered both alone and in combination with nivolumab |
| Time Frame: | Approximately 2.3 years |
| Safety Issue: | |
| Description: | |
| Measure: | Immunogenicity measured by anti-drug antibody (ADA) for BMS-986016 (all participants) and nivolumab |
| Time Frame: | Approximately 2.3 years |
| Safety Issue: | |
| Description: | |
| Measure: | QTc interval from centrally read electrocardiograms (ECGs) |
| Time Frame: | Approximately 2.3 years |
| Safety Issue: | |
| Description: | |
| Measure: | Best overall response (BOR) |
| Time Frame: | Approximately 3 years |
| Safety Issue: | |
| Description: | |
| Measure: | ORR |
| Time Frame: | Approximately 3 years |
| Safety Issue: | |
| Description: | |
| Measure: | DCR |
| Time Frame: | Approximately 3 years |
| Safety Issue: | |
| Description: | |
| Measure: | Duration of response (DOR) |
| Time Frame: | Approximately 3 years |
| Safety Issue: | |
| Description: | |
| Measure: | Progression-free survival (PFS) rates |
| Time Frame: | Up to approximately 3 years |
| Safety Issue: | |
| Description: | |
| Measure: | Overall survival (OS) |
| Time Frame: | Approximately 2 years |
| Safety Issue: | |
| Description: | |
| Measure: | Number of AEs in the Narrow Scope MedDRA Anaphylactic Reaction SMQ |
| Time Frame: | Approximately 3 years |
| Safety Issue: | |
| Description: | |
Details
| Phase: | Phase 1/Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | Bristol-Myers Squibb |
Last Updated
October 8, 2020
