Clinical trial NCT02061761: 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
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Hematologic Neoplasms
Keywords: Hodgkin lymphoma
non-Hodgkin lymphoma
diffused large B-cell lymphoma
indolent lymphoma
chronic lymphocytic leukemia
relapsed
refractory
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2014-02-13
Enrollment: 106
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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)


Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Discontinuation
timeFrame: From first dose to 100 days post last dose (Up to 51 months)
measure: Number of Participants Who Died
timeFrame: From first dose to 135 days post last dose (Up to 52 months)
measure: Number of Participants With On-Treatment Laboratory Abnormalities in Specific Hepatics Tests
timeFrame: From first dose to 30 days post last dose (Up to 49 months)
measure: Objective Response Rate (ORR) - Part D
timeFrame: 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)
measure: Duration of Response (DoR) - Part D
timeFrame: 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:
measure: BMS-986016 Maximum Observed Serum Concentration (Cmax)
timeFrame: 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
measure: BMS-986016 Time of Maximum Observed Serum Concentration (Tmax)
timeFrame: 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
measure: BMS-986016 Area Under the Concentration-time Curve in One Dosing Interval (AUC(TAU))
timeFrame: 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
measure: BMS-986016 Concentration at the End of a Dosing Interval (Ctau)
timeFrame: 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
measure: BMS-986016 Effective Elimination Half-life That Explains the Degree of AUC Accumulation Observed (T 1/2eff AUC)
timeFrame: 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
measure: BMS-986016 Total Body Clearance (CL/T)
timeFrame: 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
measure: BMS-986016 Cmax Accumulation Index (AI_Cmax)
timeFrame: 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
measure: BMS-986016 Accumulation Index (AI_AUC)
timeFrame: 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
measure: BMS-986016 Ctau Accumulation Index (AI_Ctau)
timeFrame: 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
measure: BMS-986016 Average Concentration Over a Dosing Interval ([AUC(TAU)/Tau] (Css,Avg)
timeFrame: 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
measure: BMS-986016 Trough Observed Serum Concentration (Ctrough)
timeFrame: PK assessment include the following timepoints: pre-dose, 1, 4, 24, 48, 96, 144, 192 hours end-of-infusion on cycle 1 Day 15, 29, 43, Cycle 2 Day 1, 15, 29, Cycle 3 Day 1, 15, Cycle 5 Day 1, Cycle 7 Day 1, Cycle 9 Day 1, and Cycle 11 Day 1
measure: Number of Participants With Anti-BMS-986016 Antibodies (ADA)
timeFrame: From first dose to 135 days post last dose (Up to 52 months)
measure: Number of Participants With Anti-Nivolumab Antibodies (ADA)
timeFrame: From first dose to 135 days post last dose (Up to 52 months)
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Local Institution - 0007
state: Maryland
city: Boston
country: United States
facility: Local Institution - 0004
state: Massachusetts
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Institute
state: Michigan
city: Saint Louis
country: United States
facility: Local Institution - 0010
state: Missouri
city: New York
country: United States
facility: Weill Cornell Medical College
state: New York
city: Portland
country: United States
facility: Local Institution - 0002
state: Oregon
city: Houston
country: United States
facility: Local Institution - 0006
state: Texas
city: Seattle
country: United States
facility: Local Institution - 0001
state: Washington
city: Vancouver
country: Canada
facility: Local Institution - 0011
state: British Columbia
city: Toronto
country: Canada
facility: Local Institution - 0012
state: Ontario
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
citation: 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.