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)
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
Interventions
| Drug | Synonyms | Arms |
|---|
| BMS-986016 | Anti-LAG-3 (Anti-Lymphocyte Activation Gene-3) | BMS-986016 |
| BMS-936558 | Anti-PD-1 (Anti-Programmed-Death-1) ,MDX-1106 , Nivolumab | BMS-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
| Name | Type | Description | Interventions |
|---|
| BMS-986016 | Experimental | BMS-986016 specified dose on specified days | |
| BMS-986016 + BMS-936558 | Experimental | BMS-986-016 + BMS-936558 specified dose on specified days | |
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
August 11, 2020
