Safety Study of Anti-LAG-3 With and Without Anti-PD-1 in the Treatment of Solid Tumors

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by Bristol-Myers Squibb
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT01968109
First received: September 25, 2013
Last updated: June 20, 2014
Last verified: June 2014
  Purpose

To assess the safety and tolerability, characterize the dose-limiting toxicities, and identify the maximum tolerated dose of BMS-986016 alone and in combination with Nivolumab in subjects with select advanced (metastatic and/or unresectable) solid tumors and to provide preliminary information on the clinical benefits of the combination.


Condition Intervention Phase
Neoplasms by Site
Biological: BMS-986016
Biological: BMS-936558
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1 Dose Escalation and Cohort Expansion Study of the Safety, Tolerability, and Efficacy of Anti-LAG-3 Monoclonal Antibody (BMS-986016) Administered Alone and in Combination With Anti-PD-1 Monoclonal Antibody (Nivolumab, BMS-936558) in Advanced Solid Tumors

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • Safety as measured by the rate of AEs, serious AEs, deaths and laboratory abnormalities (e.g. Grade 3 or higher per CTCAE v4) [ Time Frame: Approximately Up to 2.3 years (96 weeks of treatment period and 135 days of follow-up) ] [ Designated as safety issue: Yes ]

    CTCAE = Common Terminology Criteria for Adverse Events (AEs);

    AEs = Adverse events;

    SAEs = Serious adverse events



Secondary Outcome Measures:
  • Maximum observed serum concentration (Cmax) of BMS-986016 administered both alone and in combination with nivolumab [ Time Frame: 15 time points up through part of Cycle 3 (approximately 18 weeks) ] [ Designated as safety issue: No ]
  • Time of maximum observed serum concentration (Tmax) of BMS-986016 administered both alone and in combination with nivolumab [ Time Frame: 15 time points up through part of Cycle 3 (approximately 18 weeks) ] [ Designated as safety issue: No ]
  • Trough observed serum concentration (Ctrough) of BMS-986016 administered both alone and in combination with nivolumab [ Time Frame: 14 time points up to Cycle 12 (approximately 96 weeks) ] [ Designated as safety issue: No ]
  • Concentration at the end of a dosing interval (Ctau) [Eg: concentration at 336 hours] of BMS-986016 administered both alone and in combination with nivolumab [ Time Frame: 14 time points up to Cycle 12 (approximately 96 weeks) ] [ Designated as safety issue: No ]
  • Average concentration over a dosing interval [AUC(TAU)/tau] (Css,avg) of BMS-986016 administered both alone and in combination with nivolumab [ Time Frame: 15 time points up through part of Cycle 3 (approximately 18 weeks) ] [ Designated as safety issue: No ]
  • 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: 15 time points up through part of Cycle 3 (approximately 18 weeks) ] [ Designated as safety issue: No ]
  • Total body clearance (CLT) of BMS-986016 administered both alone and in combination with nivolumab [ Time Frame: 15 time points up through part of Cycle 3 (approximately 18 weeks) ] [ Designated as safety issue: No ]
  • Volume of distribution at steady state (Vss) of BMS-986016 administered both alone and in combination with nivolumab [ Time Frame: 15 time points up through part of Cycle 3 (approximately 18 weeks) ] [ Designated as safety issue: No ]
  • Effective elimination half-life that explains the degree of AUC accumulation observed (T-HALFeff AUC) of BMS-986016 administered both alone and in combination with nivolumab [ Time Frame: 15 time points up through part of Cycle 3 (approximately 18 weeks) ] [ Designated as safety issue: No ]
    AUC = area under the concentration-time curve

  • Effective elimination half-life that explains the degree of Cmax accumulation observed (T-HALFeff Cmax) of BMS-986016 administered both alone and in combination with nivolumab [ Time Frame: 15 time points up through part of Cycle 3 (approximately 18 weeks) ] [ Designated as safety issue: No ]
  • Accumulation index; ratio 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: 15 time points up through part of Cycle 3 (approximately 18 weeks) ] [ Designated as safety issue: No ]
  • 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: 15 time points up through part of Cycle 3 (approximately 18 weeks) ] [ Designated as safety issue: No ]
  • 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: 2 time points up through part of Cycle 3 (approximately 18 weeks) ] [ Designated as safety issue: No ]
  • DF - Degree of fluctuation or fluctuation index ([Cmax - Ctau]/Css,avg]) of BMS-986016 administered both alone and in combination with nivolumab [ Time Frame: 15 time points up through part of Cycle 3 (approximately 18 weeks) ] [ Designated as safety issue: No ]
  • Efficacy as measured by tumor assessment (irRECIST and RECIST) [ Time Frame: Every 8 weeks during treatment period (up to twelve 8-week cycles), and once during clinical follow-up period (30 days), for a total of approximately 1.9 years ] [ Designated as safety issue: No ]
    Based on immune-related Response Evaluation Criteria for Solid Tumors (irRECIST) 1.1 and Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 using Best overall response (BOR), Objective response rate (ORR), Duration of response (DOR) and Progression-free survival (PFS)

  • Immunogenicity measured by ADA for BMS-986016 (all subjects) and nivolumab (Part B & C only) [ Time Frame: 17 time points Cycle 1 through 12, up to 135 days of follow-up ] [ Designated as safety issue: No ]
  • QTc interval from centrally read electrocardiograms (ECGs) (Parts A and B) [ Time Frame: Follow-up visit 1, and Day 1 of Cycles 1 and 3 (pre-dose and 4 hour post-dose time points) ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 168
Study Start Date: October 2013
Estimated Study Completion Date: May 2018
Estimated Primary Completion Date: September 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Part A-Dose Escalation: BMS-986016
BMS-986016 20, 80, 240, and 800 mg solution intravenously, during each 8 week cycle: every 2 weeks (i.e. during weeks 1, 3, 5, 7), up to 96 weeks
Biological: BMS-986016
Other Name: Anti-LAG-3 (Anti-Lymphocyte Activation Gene-3)
Experimental: Part B-Dose Escalation: BMS-986016 + BMS-936558
BMS-986016 3, 20, 80, and 240 mg solution + BMS-936558 80 and 240 mg solution intravenously, during each 8 week cycle: every 2 weeks (i.e. during weeks 1, 3, 5, 7), up to 96 weeks
Biological: BMS-986016
Other Name: Anti-LAG-3 (Anti-Lymphocyte Activation Gene-3)
Biological: BMS-936558
Other Names:
  • Anti-PD-1 (Anti-Programmed-Death-1)
  • MDS-1106
  • Nivolumab
Experimental: Part C-Cohort Expansion: BMS-986016 + BMS-936558
BMS-986016 + BMS-936558 at doses selected in Part B, during each 8 week cycle: every 2 weeks (i.e. during weeks 1, 3, 5, 7), up to 96 weeks
Biological: BMS-986016
Other Name: Anti-LAG-3 (Anti-Lymphocyte Activation Gene-3)
Biological: BMS-936558
Other Names:
  • Anti-PD-1 (Anti-Programmed-Death-1)
  • MDS-1106
  • Nivolumab

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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

Inclusion Criteria:

  • Part A, Dose Escalation: Advanced (metastatic and/or unresectable) and incurable solid tumors, naive to Immune Cell Modulating Antibody Regimens (ICMARs)
  • Part B, Dose Escalation: Advanced (metastatic and/or unresectable) and incurable solid tumors, NSCLC subjects progressing while on- or after- receiving- anti-PD-1 or anit-PDL1 antibody as most recent therapy and melanoma subjects progressing while on- or after- receiving CTLA-4 and anti-PD-1 or PD L-1 antibody therapy (in sequential or combination regimens)
  • Part C Cohort Expansion: Advanced (metastatic and/or unresectable) and incurable: melanoma (naive to ICMARs and progressing while on- or after receiving anti-CTLA-4 and anti-PD-1 or anti-PD-L1 therapy); melanoma subjects last dose of anti-CTLA 4 therapy must be ≥ 100 days before receiving study drug medication ; non-small cell lung cancer (NSCLC) (naive to ICMARs and progressing while on- or after anti-PD-1 or anti-PD-L1 as most recent therapy) head and neck squamous cell carcinomas; or gastric adenocarcinoma naive to ICMARs
  • Part A: Progressed, or been intolerant to, at least one standard treatment regimen in the advanced or metastatic setting (if such a therapy exists)
  • Part B or C: Progressed, or been intolerant to, at least one standard treatment regimen or refuse standard treatment in the advanced or metastatic setting (if such therapy exists)
  • Received any number of prior treatment regimens
  • 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:

  • Primary central nervous system (CNS) tumors or solid tumors with CNS metastases as the only site of active disease
  • Uncontrolled CNS metastases
  • Any prior exposure to immune cell modulating antibody regimens except as described in inclusion criteria for Part B subjects or specific Part C subjects
  • Autoimmune disease
  • Encephalitis, meningitis, or uncontrolled seizures in the year prior to informed consent
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01968109

Contacts
Contact: Recruiting sites have contact information. Please contact the sites directly. If there is no contact information, please email: Clinical.Trials@bms.com
Contact: First line of the email MUST contain NCT# and Site #.

Locations
United States, Illinois
University Of Chicago Medical Center Recruiting
Chicago, Illinois, United States, 60637
Contact: Thomas F Gajewski, Site 0003    773-702-9136      
United States, Maryland
Sidney Kimmel Comprehensive Cancer Center At Johns Hopkins Recruiting
Baltimore, Maryland, United States, 21287
Contact: Charles Drake, Site 0004    410-502-9380      
United States, Massachusetts
Dana-Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Contact: F. Stephen Hodi, Site 0001    617-582-7603      
United States, New York
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Margaret Callahan, Site 0005    646-227-7101      
United States, Oregon
Providence Portland Med Ctr Recruiting
Portland, Oregon, United States, 97213
Contact: Rachel Sanborn, Site 0002    503-215-2604      
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
No publications provided

Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT01968109     History of Changes
Other Study ID Numbers: CA224-020
Study First Received: September 25, 2013
Last Updated: June 20, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Neoplasms
Neoplasms by Site
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 23, 2014