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

NCT02061761 | Completed Phase 1 Results FDA Drug

• 1 other identifier: CA224-022
• Study Type: interventional
• Target: 106
• Locations: 2 countries
• Sites: 10

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)

Conditions

Hematologic Neoplasms

Keywords

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

Outcome Measures

Primary Outcomes (5)

• 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.

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

• Number of Participants Who Died

  Number of participants who died due to any cause.

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

• 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

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

• 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.

  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)

• 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.

  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 Outcomes (13)

• BMS-986016 Maximum Observed Serum Concentration (Cmax)

  PK assessment include the following timepoints: pre-dose, 1, 4, 24, 48, 96, 144, 192 hours end-of-infusion on cycle 1 Day 1, Cycle 3 Day 1

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

  PK assessment include the following timepoints: pre-dose, 1, 4, 24, 48, 96, 144, 192 hours end-of-infusion on cycle 1 Day 1, Cycle 3 Day 1

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

  PK assessment include the following timepoints: pre-dose, 1, 4, 24, 48, 96, 144, 192 hours end-of-infusion on cycle 1 Day 1, Cycle 3 Day 1

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

  PK assessment include the following timepoints: pre-dose, 1, 4, 24, 48, 96, 144, 192 hours end-of-infusion on cycle 1 Day 1, Cycle 3 Day 1

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

  PK assessment include the following timepoints: pre-dose, 1, 4, 24, 48, 96, 144, 192 hours end-of-infusion on cycle 1 Day 1, Cycle 3 Day 1

Study Arms (4)

Part A - relatlimab (Dose escalation)

EXPERIMENTAL

Biological: BMS-986016

Part C - relatlimab + nivolumab (Dose escalation)

EXPERIMENTAL

Biological: BMS-986016; Biological: BMS-936558

Part B - relatlimab (Cohort expansion)

EXPERIMENTAL

Biological: BMS-986016

Part D - relatlimab + nivolumab (Cohort expansion)

EXPERIMENTAL

Biological: BMS-986016; Biological: BMS-936558

Interventions

BMS-986016 BIOLOGICAL

Specified Dose on Specified Days

Also known as: Anti-LAG-3 (Anti-Lymphocyte Activation Gene-3), relatlimab

Part A - relatlimab (Dose escalation); Part B - relatlimab (Cohort expansion); Part C - relatlimab + nivolumab (Dose escalation); Part D - relatlimab + nivolumab (Cohort expansion)

BMS-936558 BIOLOGICAL

Specified Dose on Specified Days

Also known as: Anti-PD-1 (Anti-Programmed-Death-1), MDX-1106, nivolumab

Part C - relatlimab + nivolumab (Dose escalation); Part D - relatlimab + nivolumab (Cohort expansion)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Bristol-Myers Squibb: lead

Study Sites (10)

Local Institution - 0007

Baltimore, Maryland, 21205, United States

Location

Local Institution - 0004

Boston, Massachusetts, 02215, United States

Location

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Local Institution - 0010

St Louis, Missouri, 63110, United States

Location

Weill Cornell Medical College

New York, New York, 10021, United States

Location

Local Institution - 0002

Portland, Oregon, 97239, United States

Location

Local Institution - 0006

Houston, Texas, 77030, United States

Location

Local Institution - 0001

Seattle, Washington, 98109, United States

Location

Local Institution - 0011

Vancouver, British Columbia, V5Z 4E6, Canada

Location

Local Institution - 0012

Toronto, Ontario, M5G 2M9, Canada

Location

Related Publications (2)

• Gopal AK, Armand P, Neelapu SS, Bartlett NL, Spurgeon SE, Kuruvilla J, Savage KJ, Leonard JP, Gelb AB, Ahmed N, Dong S, Bathena SP, Suryawanshi R, Wu JQ, Wang S, Gladstone DE. Nivolumab plus relatlimab for patients with relapsed or progressed B-cell malignancies in RELATIVITY-022. Blood Adv. 2025 Jul 8;9(13):3383-3394. doi: 10.1182/bloodadvances.2024015086.

  PMID: 40030000 DERIVED

• El Halabi L, Adam J, Gravelle P, Marty V, Danu A, Lazarovici J, Ribrag V, Bosq J, Camara-Clayette V, Laurent C, Ghez D. Expression of the Immune Checkpoint Regulators LAG-3 and TIM-3 in Classical Hodgkin Lymphoma. Clin Lymphoma Myeloma Leuk. 2021 Apr;21(4):257-266.e3. doi: 10.1016/j.clml.2020.11.009. Epub 2020 Nov 12.

  PMID: 33277223 DERIVED

Related Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting
• FDA Safety Alerts and Recalls

MeSH Terms

Conditions

Hematologic Neoplasms; Hodgkin Disease; Lymphoma, Non-Hodgkin; Leukemia, Lymphocytic, Chronic, B-Cell; Recurrence

Interventions

relatlimab; Nivolumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoma; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Bristol-Myers Squibb Study Director
• Organization: Bristol-Myers Squibb

Clinical.Trials@bms.com

Please Email

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 12, 2014
• First Posted: February 13, 2014
• Study Start: March 13, 2014
• Primary Completion: February 16, 2022
• Study Completion: February 16, 2022
• Last Updated: March 24, 2023
• Results First Posted: March 24, 2023

Record last verified: 2023-03

Locations

US (8); CA (2)