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

• ClinicalTrials.gov Identifier: NCT02061761
• Recruitment Status: Active, not recruiting
• First Posted: February 13, 2014
• Last Update Posted: October 15, 2019
• Sponsor: Bristol-Myers Squibb
• Information provided by (Responsible Party): Bristol-Myers Squibb

Study Description

Brief Summary:

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)

Condition or disease	Intervention/treatment	Phase
Hematologic Neoplasms	Biological: BMS-986016; Biological: BMS-936558	Phase 1; Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 109 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: February 25, 2014
• Estimated Primary Completion Date: May 15, 2020
• Estimated Study Completion Date: May 15, 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: BMS-986016; BMS-986016 specified dose on specified days	Biological: BMS-986016; Other Name: Anti-LAG-3 (Anti-Lymphocyte Activation Gene-3)
Experimental: BMS-986016 + BMS-936558; BMS-986-016 + BMS-936558 specified dose on specified days	Biological: BMS-986016; Other Name: Anti-LAG-3 (Anti-Lymphocyte Activation Gene-3); Biological: BMS-936558; Other Name: Anti-PD-1 (Anti-Programmed-Death-1) ,MDX-1106 , Nivolumab

Outcome Measures

Primary Outcome Measures :

1. Proportion of subjects with Adverse Events (AEs) [ Time Frame: Approximately 28 months ]
   Safety measured by incidence
2. Proportion of subjects with Serious Adverse Events (SAEs) [ Time Frame: Approximately 28 months ]
   Safety measured by incidence
3. Proportion of Deaths [ Time Frame: Approximately 28 months ]
   Safety measured by incidence
4. Proportion of subjects with clinical laboratory test abnormalities [ Time Frame: Approximately 28 months ]
   Safety measured by incidence
5. Objective response rate (ORR) [ Time Frame: Approximately 4 years ]
   Efficacy measured by proportion of treated subjects with a best overall response of complete response/complete remission (CR) or partial response/partial remission (PR)
6. Duration of Response (DOR) [ Time Frame: Approximately 4 years ]
   Efficacy measured by the duration of response for all treated subjects with a best overall response of CR or PR

Secondary Outcome Measures :

1. Maximum observed serum concentration (Cmax) of BMS-986016 administered alone and in combination with Nivolumab [ Time Frame: Approximately 28 months ]
   Pharmacokinetics (PK) measured by summary statistics
2. Time of maximum observed serum concentration (Tmax) of BMS-986016 administered both alone and in combination with Nivolumab [ Time Frame: Approximately 28 Months ]
   PK measured by summary statistics
3. Trough observed serum concentration (Ctrough) of BMS-986016 administered both alone and in combination with Nivolumab [ Time Frame: Approximately 28 Months ]
   PK measured by summary statistics
4. 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 ]
   PK measured by summary statistics
5. 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 ]
   PK measured by summary statistics
6. 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 ]
   PK measured by summary statistics
7. Total body clearance (CLT) of BMS-986016 administered both alone alone and in combination with Nivolumab [ Time Frame: Approximately 28 Months ]
   PK measured by summary statistics
8. Volume of distribution at steady state (Vss) of BMS-986016 administered both alone and in combination with Nivolumab [ Time Frame: Approximately 28 Months ]
   PK measured by summary statistics
9. 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 ]
   PK measured by summary statistics
10. 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 ]
    PK measured by summary statistics
11. 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 ]
    PK measured by summary statistics
12. 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 ]
    PK measured by summary statistics
13. 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 ]
    PK measured by summary statistics
14. 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 ]
    PK measured by summary statistics
15. Incidence of ADA to nivolumab and BMS-986016 [ Time Frame: Approximately 28 Months ]
    Immunogenicity measured by summary statistics
16. Summary of AEs of special interest by [ Time Frame: Approximately 28 Months ]
    Immunogenicity measured by summary statistics

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, Maryland

The Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, United States, 21287

United States, Massachusetts

Dana Farber Cancer Institute

Boston, Massachusetts, United States, 02215

United States, Michigan

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, United States, 48201

United States, Missouri

Washington University School Of Medicine

Saint Louis, Missouri, United States, 63110

United States, New York

Weill Cornell Medical College

New York, New York, United States, 10021

United States, Oregon

Oregon Health & Science University

Portland, Oregon, United States, 97239

United States, Texas

MD Anderson Cancer Center

Houston, Texas, United States, 77030

United States, Washington

University of Washington

Seattle, Washington, United States, 98109

Canada, British Columbia

BC Cancer Agency - Vancouver Centre

Vancouver, British Columbia, Canada, V5Z 4E6

Canada, Ontario

University Health Network - Princess Margaret Cancer Centre

Toronto, Ontario, Canada, M5G 2M9

Sponsors and Collaborators

Bristol-Myers Squibb

Investigators

• Study Director: Bristol-Myers Squibb; Bristol-Myers Squibb

More Information

Additional Information:

BMS Clinical Trial Information 

BMS Clinical Trial Patient Recruiting 

Investigator Inquiry Form 

FDA Safety Alerts and Recalls 

• Responsible Party: Bristol-Myers Squibb
• ClinicalTrials.gov Identifier: NCT02061761
• Other Study ID Numbers: CA224-022
• First Posted: February 13, 2014
• Last Update Posted: October 15, 2019
• Last Verified: October 2019

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Hematologic Neoplasms; Neoplasms; Neoplasms by Site; Hematologic Diseases; Nivolumab; Antineoplastic Agents, Immunological; Antineoplastic Agents