Clinical Trials /

Safety Study of Anti-LAG-3 in Relapsed or Refractory Hematologic Malignancies

NCT02061761

Description:

The primary objective of this study is to characterize the safety, tolerability and maximum tolerated dose of BMS-986016 administered alone or in combination with Nivolumab to subjects with relapsed hematologic malignancies. Co-primary objective is to investigate the preliminary efficacy of BMS-986016 in combination with nivolumab in subjects with relapsed or refractory Hodgkin lymphoma (HL), and relapsed or refractory Diffuse Large B Cell lymphoma (DLBCL)

Related Conditions:
  • Chronic Lymphocytic Leukemia
  • Diffuse Large B-Cell Lymphoma
  • Hodgkin Lymphoma
  • Multiple Myeloma
  • Non-Hodgkin Lymphoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: CA224-022
  • NCT ID: NCT02061761

Conditions

  • Hematologic Neoplasms

Interventions

DrugSynonymsArms
BMS-986016Anti-LAG-3 (Anti-Lymphocyte Activation Gene-3)BMS-986016
BMS-936558Anti-PD-1 (Anti-Programmed-Death-1) ,MDX-1106 , NivolumabBMS-986016 + BMS-936558

Purpose

The primary objective of this study is to characterize the safety, tolerability and maximum tolerated dose of BMS-986016 administered alone or in combination with Nivolumab to subjects with relapsed hematologic malignancies. Co-primary objective is to investigate the preliminary efficacy of BMS-986016 in combination with nivolumab in subjects with relapsed or refractory Hodgkin lymphoma (HL), and relapsed or refractory Diffuse Large B Cell lymphoma (DLBCL)

Trial Arms

NameTypeDescriptionInterventions
BMS-986016ExperimentalBMS-986016 specified dose on specified days
  • BMS-986016
BMS-986016 + BMS-936558ExperimentalBMS-986-016 + BMS-936558 specified dose on specified days
  • BMS-986016
  • BMS-936558

Eligibility Criteria

        For more information regarding BMS clinical trial participation, please visit
        www.BMSStudyConnect.com

        Inclusion Criteria:

          -  For dose escalation monotherapy: CLL, HL, NHL, MM

          -  For dose expansion monotherapy: CLL, HL, NHL

          -  For dose escalation and dose expansion in combination with BMS-936558: HL and DLBCL

          -  Progressed, or been intolerant to, at least one standard treatment regimen

          -  Not eligible for or declined transplantation or any standard therapy known to be life
             prolonging or life saving

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

          -  At least 1 lesion with measurable disease at baseline

          -  Availability of an existing tumor biopsy sample (or consent to allow pre-treatment
             tumor biopsy if sample not available)

        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)

          -  Autoimmune disease

          -  Encephalitis, meningitis, or uncontrolled seizures in the year prior to informed
             consent

          -  Uncontrolled or significant cardiovascular disease

        Other protocol defined inclusion/exclusion criteria could apply
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Proportion of subjects with Adverse Events (AEs)
Time Frame:Approximately 28 months
Safety Issue:
Description:Safety measured by incidence

Secondary Outcome Measures

Measure:Maximum observed serum concentration (Cmax) of BMS-986016 administered alone and in combination with Nivolumab
Time Frame:Approximately 28 months
Safety Issue:
Description:Pharmacokinetics (PK) measured by summary statistics
Measure:Time of maximum observed serum concentration (Tmax) of BMS-986016 administered both alone and in combination with Nivolumab
Time Frame:Approximately 28 Months
Safety Issue:
Description:PK measured by summary statistics
Measure:Trough observed serum concentration (Ctrough) of BMS-986016 administered both alone and in combination with Nivolumab
Time Frame:Approximately 28 Months
Safety Issue:
Description:PK measured by summary statistics
Measure:Concentration at the end of a dosing interval (Ctau) of BMS-986016 administered both alone and in combination with Nivolumab
Time Frame:Approximately 28 Months
Safety Issue:
Description:PK measured by summary statistics
Measure:Average concentration over a dosing interval [AUC(TAU)/tau] (Css,avg) of BMS-986016 administered both alone and in combination with Nivolumab
Time Frame:Approximately 28 Months
Safety Issue:
Description:PK measured by summary statistics
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 28 Months
Safety Issue:
Description:PK measured by summary statistics
Measure:Total body clearance (CLT) of BMS-986016 administered both alone alone and in combination with Nivolumab
Time Frame:Approximately 28 Months
Safety Issue:
Description:PK measured by summary statistics
Measure:Volume of distribution at steady state (Vss) of BMS-986016 administered both alone and in combination with Nivolumab
Time Frame:Approximately 28 Months
Safety Issue:
Description:PK measured by summary statistics
Measure:Effective elimination half-life that explains the degree of AUC administered alone accumulation observed (T-HALFeff AUC) of BMS-986016 administered both alone and in combination with Nivolumab
Time Frame:Approximately 28 Months
Safety Issue:
Description:PK measured by summary statistics
Measure:Effective elimination half-life that explains the degree of Cmax administered alone accumulation observed (T-HALFeff Cmax) of BMS-986016 administered both alone and in combination with Nivolumab
Time Frame:Approximately 28 Months
Safety Issue:
Description:PK measured by summary statistics
Measure:Accumulation index; ration 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 28 Months
Safety Issue:
Description:PK measured by summary statistics
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 28 Months
Safety Issue:
Description:PK measured by summary statistics
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 28 Months
Safety Issue:
Description:PK measured by summary statistics
Measure:Degree of fluctuation or fluctuation index ([Cmax - Ctau]/Css,avg) (DF) of BMS-986016 administered both alone and in combination with Nivolumab
Time Frame:Approximately 28 Months
Safety Issue:
Description:PK measured by summary statistics
Measure:Incidence of ADA to nivolumab and BMS-986016
Time Frame:Approximately 28 Months
Safety Issue:
Description:Immunogenicity measured by summary statistics
Measure:Summary of AEs of special interest by
Time Frame:Approximately 28 Months
Safety Issue:
Description:Immunogenicity measured by summary statistics

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:Bristol-Myers Squibb

Last Updated

October 14, 2019