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A Study to Evaluate the Safety, Tolerability, and Efficacy of Relatlimab in Relapsed or Refractory B-Cell Malignancies

Primary Purpose

Hematologic Neoplasms

Status

Completed

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

BMS-986016

BMS-936558

About this trial

This is an interventional treatment trial for Hematologic Neoplasms focused on measuring Hodgkin lymphoma, non-Hodgkin lymphoma, diffused large B-cell lymphoma, indolent lymphoma, chronic lymphocytic leukemia, relapsed, refractory

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Must have histologic or cytologic confirmation of chronic lymphocytic leukemia, Hodgkin lymphoma, Non-Hodgkin lymphoma, or Multiple Myeloma and have relapsed following prior treatment or been refractory to prior treatment
Must have progressed or been refractory to, at least one prior standard therapy, including radiation, immunomodulatory agents (eg, lenalidomide), immunotherapy, cytotoxic chemotherapy, and select antibody (anti-CD20, alemtuzumab, or anti-CD30) therapy.
Must be more than 100 days post autologous transplant

Exclusion Criteria:

Known or suspected central nervous system (CNS) metastases or with the CNS as the only site of active disease (controlled CNS metastases are allowed)
Known or suspected autoimmune disease
History of allergy to anti-PD-1 or anti-PD-L1 antibody therapy or to other monoclonal antibodies or related compounds or to any of their components

Other protocol-defined inclusion/exclusion criteria apply

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Arm Label

Part A - relatlimab (Dose escalation)

Part C - relatlimab + nivolumab (Dose escalation)

Part B - relatlimab (Cohort expansion)

Part D - relatlimab + nivolumab (Cohort expansion)

Arm Description

Outcomes

Primary Outcome Measures

Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Discontinuation

Number of participants with any grade adverse events (AEs), any grade serious adverse events (SAEs) and any grade AEs leading to discontinuation of any drug. The severity of AEs will be graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. An AE is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment.

Number of Participants Who Died

Number of participants who died due to any cause.

Number of Participants With On-Treatment Laboratory Abnormalities in Specific Hepatics Tests

Number of participants with laboratory abnormalities in specific hepatic tests based on SI unit convention. The number of participants with the following laboratory abnormalities from on-treatment evaluations will be summarized: ALT or AST > 3 x ULN, > 5 x ULN, > 10 x ULN and > 20 x ULN Total bilirubin > 2 x ULN ALP > 1.5 x ULN Concurrent (within 1 day) ALT or AST > 3 x ULN and total bilirubin > 1.5 x ULN Concurrent (within 30 days) ALT or AST > 3 x ULN and total bilirubin > 1.5 x ULN Concurrent (within 1 day) ALT or AST > 3 x ULN and total bilirubin > 2 x ULN Concurrent (within 30 days) ALT or AST > 3 x ULN and total bilirubin > 2 x ULN

Objective Response Rate (ORR) - Part D

Investigator-assessed ORR per International Working Group (IWG 2007) response criteria for malignant lymphoma is defined as the number of participants with a best overall documented response (BOR) of either a complete response (CR) or partial response (PR). Complete response: Disappearance of all evidence of disease. Partial response: Regression of measurable disease and no new sites. >= 50% decrease in sum of the produce of the diameters of up to 6 largest dominant masses (index lesions); no increase in size of other nodes (non-index lesions). Progressive disease: Any new lesion or increase by >=50% of previously involved sites from nadir.

Duration of Response (DoR) - Part D

Investigator-assessed DoR per International Working Group (IWG 2007)) response criteria for malignant lymphoma is defined as the time between the date of first documented response (complete response or partial response) to the date of the first objectively documented progression, or death due to any cause, whichever occurs first. Complete response: Disappearance of all evidence of disease. Partial response: Regression of measurable disease and no new sites. >= 50% decrease in sum of the produce of the diameters of up to 6 largest dominant masses (index lesions); no increase in size of other nodes (non-index lesions). Progressive disease: Any new lesion or increase by >=50% of previously involved sites from nadir.

Secondary Outcome Measures

BMS-986016 Maximum Observed Serum Concentration (Cmax)

BMS-986016 Maximum Observed Serum Concentration (Cmax). Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (% CV) is being reported. Period 0 = treatment period Period 1 = Re-challenge period

BMS-986016 Time of Maximum Observed Serum Concentration (Tmax)

BMS-986016 Time of Maximum Observed Serum Concentration (Tmax). Period 0 = treatment period Period 1 = Re-challenge period

BMS-986016 Area Under the Concentration-time Curve in One Dosing Interval (AUC(TAU))

BMS-986016 Area under the concentration-time curve in one dosing interval (AUC(TAU)). Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (% CV) is being reported. Period 0 = treatment period Period 1 = Re-challenge period

BMS-986016 Concentration at the End of a Dosing Interval (Ctau)

BMS-986016 Concentration at the end of a dosing interval (Ctau). Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (% CV) is being reported. Period 0 = treatment period Period 1 = Re-challenge period

BMS-986016 Effective Elimination Half-life That Explains the Degree of AUC Accumulation Observed (T 1/2eff AUC)

BMS-986016 effective elimination half-life that explains the degree of AUC accumulation observed (t 1/2eff AUC). Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (% CV) is being reported. Period 0 = treatment period Period 1 = Re-challenge period

BMS-986016 Total Body Clearance (CL/T)

BMS-986016 total body clearance (CL/T). Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (% CV) is being reported. Period 0 = treatment period Period 1 = Re-challenge period

BMS-986016 Cmax Accumulation Index (AI_Cmax)

BMS-986016 cmax accumulation index (AI_Cmax). AI is calculated based on ratio of Cmax at steady state to Cmax after the first dose. Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (% CV) is being reported. Period 0 = treatment period Period 1 - Re-challenge period

BMS-986016 Accumulation Index (AI_AUC)

BMS-986016 accumulation index (AI_AUC). AI is calculated based on ratio of AUC(TAU) at steady state to AUC(TAU) after the first dose. Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (% CV) is being reported. Period 0 = treatment period Period 1 - Re-challenge period

BMS-986016 Ctau Accumulation Index (AI_Ctau)

BMS-986016 Ctau accumulation index (AI_Ctau). AI is calculated based on ratio of Ctau at steady state to Ctau after the first dose. Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (% CV) is being reported. Period 0 = treatment period Period 1 - Re-challenge period

BMS-986016 Average Concentration Over a Dosing Interval ([AUC(TAU)/Tau] (Css,Avg)

BMS-986016 average concentration over a dosing interval ([AUC(TAU)/tau] (Css,avg). Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (% CV) is being reported. Period 0 = treatment period Period 1 - Re-challenge period

BMS-986016 Trough Observed Serum Concentration (Ctrough)

BMS-986016 trough observed serum concentration (Ctrough). Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (% CV) is being reported. Period 0 = treatment period Period 1 - Re-challenge period

Number of Participants With Anti-BMS-986016 Antibodies (ADA)

Number of participants with anti-BMS-986016 antibodies (ADA) with status as baseline ADA positive, ADA positive and ADA negative. Baseline ADA positive participant is defined as a participant with positive seroconversion detected in the last sample before initiation of treatment. ADA-positive participant is a participant with at least one ADA-positive sample relative to baseline after initiation of the treatment. ADA negative participant is defined as a participant with no ADA positive sample after the initiation of treatment.

Number of Participants With Anti-Nivolumab Antibodies (ADA)

Number of participants with anti-Nivolumab antibodies (ADA) with status as baseline ADA positive, ADA positive and ADA negative. Baseline ADA positive participant is defined as a participant with positive seroconversion detected in the last sample before initiation of treatment. ADA-positive participant is a participant with at least one ADA-positive sample relative to baseline after initiation of the treatment. ADA negative participant is defined as a participant with no ADA positive sample after the initiation of treatment.

Full Information

NCT ID

NCT02061761

First Posted

February 12, 2014

Last Updated

March 20, 2023

Sponsor

Bristol-Myers Squibb

1. Study Identification

Unique Protocol Identification Number

NCT02061761

Brief Title

A Study to Evaluate the Safety, Tolerability, and Efficacy of Relatlimab in Relapsed or Refractory B-Cell Malignancies

Official Title

A Phase 1/2a Dose Escalation and Cohort Expansion Study of the Safety, Tolerability, and Efficacy of Anti-LAG-3 Monoclonal Antibody (Relatlimab, BMS-986016) Administered Alone and in Combination With Anti-PD-1 Monoclonal Antibody (Nivolumab, BMS-936558) in Relapsed or Refractory B-Cell Malignancies

Study Type

Interventional

2. Study Status

Record Verification Date

March 2023

Overall Recruitment Status

Completed

Study Start Date

March 13, 2014 (Actual)

Primary Completion Date

February 16, 2022 (Actual)

Study Completion Date

February 16, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Bristol-Myers Squibb

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

The primary objective of this study is to characterize the safety, tolerability, dose-limiting toxicities (DLTs), and maximum tolerated dose (MTD) of relatlimab administered alone or in combination with nivolumab to subjects with relapsed or refractory B-cell malignancies. Co-primary objective is to investigate the preliminary efficacy of relatlimab in combination with nivolumab in subjects with relapsed or refractory Hodgkin lymphoma (HL), and relapsed or refractory Diffused Large B Cell lymphoma (DLBCL)

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hematologic Neoplasms

Keywords

Hodgkin lymphoma, non-Hodgkin lymphoma, diffused large B-cell lymphoma, indolent lymphoma, chronic lymphocytic leukemia, relapsed, refractory

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

106 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Part A - relatlimab (Dose escalation)

Arm Type

Experimental

Arm Title

Part C - relatlimab + nivolumab (Dose escalation)

Arm Type

Experimental

Arm Title

Part B - relatlimab (Cohort expansion)

Arm Type

Experimental

Arm Title

Part D - relatlimab + nivolumab (Cohort expansion)

Arm Type

Experimental

Intervention Type

Biological

Intervention Name(s)

BMS-986016

Other Intervention Name(s)

Anti-LAG-3 (Anti-Lymphocyte Activation Gene-3), relatlimab

Intervention Description

Specified Dose on Specified Days

Intervention Type

Biological

Intervention Name(s)

BMS-936558

Other Intervention Name(s)

Anti-PD-1 (Anti-Programmed-Death-1), MDX-1106, nivolumab

Intervention Description

Specified Dose on Specified Days

Primary Outcome Measure Information:

Title

Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Discontinuation

Description

Time Frame

From first dose to 100 days post last dose (Up to 51 months)

Title

Number of Participants Who Died

Description

Number of participants who died due to any cause.

Time Frame

From first dose to 135 days post last dose (Up to 52 months)

Title

Number of Participants With On-Treatment Laboratory Abnormalities in Specific Hepatics Tests

Description

Time Frame

From first dose to 30 days post last dose (Up to 49 months)

Title

Objective Response Rate (ORR) - Part D

Description

Time Frame

From first dose date to the date of disease progression per investigator or the date of subsequent therapy, whichever occurs first (Up to approximately 95 months)

Title

Duration of Response (DoR) - Part D

Description

Time Frame

From first dose to the date of the first objectively documented progression, or death due to any cause, whichever occurs first (Up to approximately 95 months)

Secondary Outcome Measure Information:

Title

BMS-986016 Maximum Observed Serum Concentration (Cmax)

Description

Time Frame