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 March 2016 by Bristol-Myers Squibb
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT01968109
First received: September 25, 2013
Last updated: July 26, 2016
Last verified: March 2016
  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 I/2a 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 4 years ] [ 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: Approximately 2.3 years ] [ 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: Approximately 2.3 years ] [ Designated as safety issue: No ]
  • Trough observed serum concentration (Ctrough) of BMS-986016 administered both alone and in combination with nivolumab [ Time Frame: Approximately 2.3 years ] [ 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: Approximately 2.3 years ] [ 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: Approximately 2.3 years ] [ 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: Approximately 2.3 years ] [ Designated as safety issue: No ]
  • Total body clearance (CLT) of BMS-986016 administered both alone and in combination with nivolumab [ Time Frame: Approximately 2.3 years ] [ 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: Approximately 2.3 years ] [ 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: Approximately 2.3 years ] [ 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: Approximately 2.3 years ] [ 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: Approximately 2.3 years ] [ 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: Approximately 2.3 years ] [ 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: Approximately 2.3 years ] [ Designated as safety issue: No ]
  • Degree of fluctuation (DF) or fluctuation index ([Cmax - Ctau]/Css,avg]) of BMS-986016 administered both alone and in combination with nivolumab [ Time Frame: Approximately 2.3 years ] [ Designated as safety issue: No ]
  • Efficacy as measured by tumor assessment (irRECIST and RECIST) [ Time Frame: Approximately 4 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 [ Time Frame: Approximately 2.3 years ] [ Designated as safety issue: No ]
    Timeframe: Up to 1.8 years + 135 days posttreatment follow-up (total of up to approximately 2.3 years)

  • QTc interval from centrally read electrocardiograms (ECGs) [ Time Frame: up to 12 eight-week cycles ] [ Designated as safety issue: Yes ]
  • Best overall response (BOR) [ Time Frame: Approximately 4 years ] [ Designated as safety issue: No ]
  • Objective response rate (ORR) [ Time Frame: Approximately 4 years ] [ Designated as safety issue: No ]
  • Disease control rate (DCR) [ Time Frame: Approximately 4 years ] [ Designated as safety issue: No ]
  • Duration of response (DOR) [ Time Frame: Approximately 4 years ] [ Designated as safety issue: No ]
  • Progression-free survival (PFS) [ Time Frame: Approximately 4 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 360
Study Start Date: October 2013
Estimated Study Completion Date: May 2018
Estimated Primary Completion Date: May 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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-986016 + BMS-936558 specified dose on specified days
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)
  • MDX-1106
  • Nivolumab

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
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:

  • For Dose escalation: subjects with cervical, ovarian, bladder and CRC, head and neck, gastric and hepatocellular cancer naive to immuno-oncology agents; 1st line melanoma and NSCLC; Renal Cell Carcinoma naive to IO; NSCLC progressing while on or after therapy with anti-PD1/anti-PDL-1 and melanoma subjects progressed while-on or after treatment with anti-PD1 or anti-PDL1 with or without anti-CTLA-4.
  • For Dose Expansion: all of the above in escalation except for cervical, ovarian bladder and CRC
  • Progressed, or been intolerant to, at least one standard treatment regimen
  • Received any number of prior treatment regimens
  • 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
  • Autoimmune disease
  • Encephalitis, meningitis, or uncontrolled seizures in the year prior to informed consent
  • Uncontrolled CNS metastases
  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 Gajewski, Site 0003    773-702-2085      
United States, Maryland
Sidney Kimmel Comprehensive Cancer Center At Johns Hopkins Recruiting
Baltimore, Maryland, United States, 21287
Contact: Evan Lipson, 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, Michigan
Local Institution Not yet recruiting
Detroit, Michigan, United States, 48201
Contact: Site 0011         
United States, New York
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Margaret Callahan, Site 0005    646-888-3359      
United States, Oregon
Providence Portland Med Ctr Recruiting
Portland, Oregon, United States, 97213
Contact: Rachel Sanborn, Site 0002    503-215-2604      
United States, Pennsylvania
Local Institution Not yet recruiting
Pittsburgh, Pennsylvania, United States, 15232
Contact: Site 0010         
United States, Washington
Local Institution Not yet recruiting
Seattle, Washington, United States, 98109
Contact: Site 0008         
Denmark
Local Institution Not yet recruiting
Copenhagen, Denmark, 2100
Contact: Site 0028         
Finland
Local Institution Recruiting
Helsinki, Finland, 00029
Contact: Site 0021         
Italy
Local Institution Not yet recruiting
Milano, Italy, 20141
Contact: Site 0014         
Local Institution Not yet recruiting
Napoli, Italy, 80131
Contact: Site 0013         
Spain
Local Institution Recruiting
Barcelona, Spain, 08035
Contact: Site 0015         
Local Institution Recruiting
Pamplona, Spain, 31008
Contact: Site 0006         
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT01968109     History of Changes
Other Study ID Numbers: CA224-020  2014-002605-38 
Study First Received: September 25, 2013
Last Updated: July 26, 2016
Health Authority: United States: Food and Drug Administration
Spain: Spanish Agency of Medicines
Germany: Federal Institute for Drugs and Medical Devices
Italy: Ministry of Health
Italy: National Bioethics Committee
Italy: National Institute of Health
Italy: National Monitoring Centre for Clinical Trials - Ministry of Health
Italy: The Italian Medicines Agency
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Finland: Finnish Medicines Agency
Finland: Data Protection Board
Finland: National Advisory Board on Health Care Ethics
Norway: Data Protection Authority
Norway: Directorate of Health
Norway: Norwegian Medicines Agency
Norway:National Committee for Medical and Health Research Ethics
Switzerland: Swissmedic
Austria: Federal Office for Safety in Health Care
Denmark: Danish Dataprotection Agency
Denmark: Danish Medicines Agency
Denmark: The Danish National Committee on Biomedical Research Ethics

Additional relevant MeSH terms:
Neoplasms by Site
Neoplasms
Nivolumab
Antibodies, Monoclonal
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 27, 2016