Neoplasms

Blood and Lymph Conditions

All Conditions

Immune System Diseases

Symptoms and General Pathology

Rare Diseases

Leukemia

Leukemia, Lymphoid

Lymphoma

Hematologic Neoplasms

Leukemia, Lymphocytic, Chronic, B-Cell

Hodgkin Disease

Lymphoma, B-Cell

Hematologic Diseases

B-cell Lymphoma

Chronic Graft Versus Host Disease

Lymphosarcoma

Chronic Lymphocytic Leukemia

Hodgkin Lymphoma

Antineoplastic Agents

All Drugs and Chemicals

Nivolumab

Antibodies

Antibodies, Monoclonal

Relatlimab

Immunoglobulins

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

BMS-986016

BMS-936558

Bristol-Myers Squibb

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)

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

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

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 due to any cause.

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

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.

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.

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). Period 0 = treatment period Period 1 = Re-challenge period

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). 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). 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). 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). 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). 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). 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). 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). 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) 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) 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.

Dose escalation (part A): BMS-986016 800mg up to twelve 8-week treatment cycles, confirmed progressive disease, or until meeting criteria for discontinuation, whichever occurs first. Each treatment cycle comprises 4 doses of BMS-986016 administered on days 1, 15, 29, and 43. Participants could further receive therapy for up to 6 additional eight-week cycles if re-challenge period criteria are met.

All Mono Esc 20 Q2W

All Mono Esc 80 Q2W

All Mono Esc 240 Q2W

All Mono Esc 800 Q2W

Dose expansion (part B): BMS-986016 240mg up to twelve 8-week treatment cycles, confirmed progressive disease, or until meeting criteria for discontinuation, whichever occurs first. Each treatment cycle comprises 4 doses of BMS-986016 administered on days 1, 15, 29, and 43. Participants could further receive therapy for up to 6 additional eight-week cycles if re-challenge period criteria are met.

CLL BMS-986016 240mg

DLBCL BMS-986016 240mg

iNHL BMS-986016 240mg

HL BMS-986016 240mg

Dose escalation (part C): BMS-986016 IV 80mg + Nivolumab IV 240mg up to twelve 8-week treatment cycles, confirmed progressive disease, or until meeting criteria for discontinuation, whichever occurs first. Each treatment cycle comprises 4 doses of Nivolumab followed by BMS-986016 on days 1, 15, 29, and 43. Participants could further receive therapy for up to 6 additional eight-week cycles if re-challenge period criteria are met.

All Combo Esc 80/240 Q2W

Dose escalation (part C): BMS-986016 IV 160mg + Nivolumab IV 240mg up to twelve 8-week treatment cycles, confirmed progressive disease, or until meeting criteria for discontinuation, whichever occurs first. Each treatment cycle comprises 4 doses of Nivolumab followed by BMS-986016 on days 1, 15, 29, and 43. Participants could further receive therapy for up to 6 additional eight-week cycles if re-challenge period criteria are met.

All Combo Esc 160/240 Q2W

Dose escalation (part C): BMS-986016 IV 240mg + Nivolumab IV 240mg up to twelve 8-week treatment cycles, confirmed progressive disease, or until meeting criteria for discontinuation, whichever occurs first. Each treatment cycle comprises 4 doses of Nivolumab followed by BMS-986016 on days 1, 15, 29, and 43. Participants could further receive therapy for up to 6 additional eight-week cycles if re-challenge period criteria are met.

All Combo Esc 240/240 Q2W

Dose expansion (part D): BMS-986016 IV 160mg + Nivolumab IV 240mg up to twelve 8-week treatment cycles, confirmed progressive disease, or until meeting criteria for discontinuation, whichever occurs first. Each treatment cycle comprises 4 doses of Nivolumab followed by BMS-986016 on days 1, 15, 29, and 43. Participants could further receive therapy for up to 6 additional eight-week cycles if re-challenge period criteria are met.

HL Naive BMS-986016 160mg + Nivolumab

DLBCL BMS-986016 160mg + Nivolumab

HL Post I/O BMS-986016 160mg + Nivolumab

Dose escalation (part A): BMS-986016 20mg up to twelve 8-week treatment cycles, confirmed progressive disease, until meeting criteria for discontinuation, or clinical deterioration, whichever occurs first. Each treatment cycle comprises 4 doses of BMS-986016 administered on days 1, 15, 29, and 43. Participants could further receive therapy for up to 6 additional eight-week cycles if re-challenge period criteria are met.

BMS-986016 20mg

Dose escalation (part A): BMS-986016 800mg up to twelve 8-week treatment cycles, confirmed progressive disease, until meeting criteria for discontinuation, or clinical deterioration, whichever occurs first. Each treatment cycle comprises 4 doses of BMS-986016 administered on days 1, 15, 29, and 43. Participants could further receive therapy for up to 6 additional eight-week cycles if re-challenge period criteria are met.

BMS-986016 800mg

Dose escalation (part A): BMS-986016 80mg up to twelve 8-week treatment cycles, confirmed progressive disease, until meeting criteria for discontinuation, or clinical deterioration, whichever occurs first. Each treatment cycle comprises 4 doses of BMS-986016 administered on days 1, 15, 29, and 43. Participants could further receive therapy for up to 6 additional eight-week cycles if re-challenge period criteria are met.

BMS-986016 80mg

Dose escalation (part A) and dose expansion (part B): BMS-986016 240mg up to twelve 8-week treatment cycles, confirmed progressive disease, until meeting criteria for discontinuation, or clinical deterioration, whichever occurs first. Each treatment cycle comprises 4 doses of BMS-986016 administered on days 1, 15, 29, and 43. Participants could further receive therapy for up to 6 additional eight-week cycles if re-challenge period criteria are met.

BMS-986016 240mg

Dose escalation (part C): BMS-986016 IV 80mg + Nivolumab IV 240mg up to twelve 8-week treatment cycles, confirmed progressive disease, until meeting criteria for discontinuation, or clinical deterioration, whichever occurs first. Each treatment cycle comprises 4 doses of Nivolumab followed by BMS-986016 on days 1, 15, 29, and 43. Participants could further receive therapy for up to 6 additional eight-week cycles if re-challenge period criteria are met.

BMS-986016 80mg + Nivolumab

Dose escalation (part C): BMS-986016 IV 240mg + Nivolumab IV 240mg up to twelve 8-week treatment cycles, confirmed progressive disease, until meeting criteria for discontinuation, or clinical deterioration, whichever occurs first. Each treatment cycle comprises 4 doses of Nivolumab followed by BMS-986016 on days 1, 15, 29, and 43. Participants could further receive therapy for up to 6 additional eight-week cycles if re-challenge period criteria are met.

BMS-986016 240mg + Nivolumab

Dose escalation (part C) and dose expansion (part D): BMS-986016 IV 160mg + Nivolumab IV 240mg up to twelve 8-week treatment cycles, confirmed progressive disease, until meeting criteria for discontinuation, or clinical deterioration, whichever occurs first. Each treatment cycle comprises 4 doses of Nivolumab followed by BMS-986016 on days 1, 15, 29, and 43. Participants could further receive therapy for up to 6 additional eight-week cycles if re-challenge period criteria are met.

BMS-986016 160mg + Nivolumab

Total

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Bristol-Myers Squibb Study Director

SAEs

AEs leading to discontinuation

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

Number of Participants Who Died

ALT OR AST > 3XULN

ALT OR AST > 5XULN

ALT OR AST > 10XULN

ALT OR AST > 20XULN

TOTAL BILIRUBIN > 2XULN

ALP > 1.5XULN

CONCURRENT ALT OR AST ELEVATION > 3XULN WITH TOTAL BILIRUBIN > 1.5XULN WITHIN ONE DAY

CONCURRENT ALT OR AST ELEVATION > 3XULN WITH TOTAL BILIRUBIN > 1.5XULN WITHIN 30 DAYS

CONCURRENT ALT OR AST ELEVATION > 3XULN WITH TOTAL BILIRUBIN > 2XULN WITHIN ONE DAY

CONCURRENT ALT OR AST ELEVATION > 3XULN WITH TOTAL BILIRUBIN > 2XULN WITHIN 30 DAYS

All treated participants with at least one on-treatment measurement of the corresponding laboratory parameter

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

Pre-specified only to be collected in all treated participants by tumor type for Part D

Objective Response Rate (ORR) - Part D

Pre-specified only to be collected in all responders (CR or PR) by tumor type for Part D

Duration of Response (DoR) - Part D

Period 0, Cycle 1, Day 1 (P0C1D1)

P0C3D1

P1C1D1

P1C3D1

All participants who received at least one dose of BMS-986016 and have evaluable serum concentration data

BMS-986016 Maximum Observed Serum Concentration (Cmax)

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

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

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

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

BMS-986016 Total Body Clearance (CL/T)

BMS-986016 Cmax Accumulation Index (AI_Cmax)

BMS-986016 Accumulation Index (AI_AUC)

BMS-986016 Ctau Accumulation Index (AI_Ctau)

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

P0C1D15

P0C1D29

P0C1D43

P0C2D1

P0C2D15

P0C2D29

P0C3D15

P0C5D1

P0C7D1

P0C9D1

P0C11D1

P1C1D15

P1C1D29

P1C1D43

P1C2D1

P1C2D15

P1C2D29

P1C3D15

P1C5D1

P1C7D1

P1C9D1

P1C11D1

BMS-986016 Trough Observed Serum Concentration (Ctrough)

Baseline ADA Positive

ADA Positive

ADA Negative

All BMS-986016 treated participants with baseline and at least one post-baseline assessment

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

All Nivolumab treated participants with baseline and at least one post-baseline assessment

Number of Participants With Anti-Nivolumab Antibodies (ADA)

Dose escalation (part A): BMS-986016 240mg up to twelve 8-week treatment cycles, confirmed progressive disease, until meeting criteria for discontinuation, or clinical deterioration, whichever occurs first. Each treatment cycle comprises 4 doses of BMS-986016 administered on days 1, 15, 29, and 43. Participants could further receive therapy for up to 6 additional eight-week cycles if re-challenge period criteria are met.

Dose expansion (part B): BMS-986016 240mg up to twelve 8-week treatment cycles, confirmed progressive disease, until meeting criteria for discontinuation, or clinical deterioration, whichever occurs first. Each treatment cycle comprises 4 doses of BMS-986016 administered on days 1, 15, 29, and 43. Participants could further receive therapy for up to 6 additional eight-week cycles if re-challenge period criteria are met.

BMS-986016 240mg Part B

Dose escalation (part C): BMS-986016 IV 160mg + Nivolumab IV 240mg up to twelve 8-week treatment cycles, confirmed progressive disease, until meeting criteria for discontinuation, or clinical deterioration, whichever occurs first. Each treatment cycle comprises 4 doses of Nivolumab followed by BMS-986016 on days 1, 15, 29, and 43. Participants could further receive therapy for up to 6 additional eight-week cycles if re-challenge period criteria are met.

Dose expansion (part D): BMS-986016 IV 160mg + Nivolumab IV 240mg up to twelve 8-week treatment cycles, confirmed progressive disease, until meeting criteria for discontinuation, or clinical deterioration, whichever occurs first. Each treatment cycle comprises 4 doses of Nivolumab followed by BMS-986016 on days 1, 15, 29, and 43. Participants could further receive therapy for up to 6 additional eight-week cycles if re-challenge period criteria are met.

Spots Global Cancer Trial Database for A Study to Evaluate the Safety, Tolerability, and Efficacy of Relatlimab in Relapsed or Refractory B-Cell Malignancies

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

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