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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 January 2017 by Bristol-Myers Squibb
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT01968109
First received: September 25, 2013
Last updated: January 27, 2017
Last verified: January 2017
  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
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: No masking
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:
  • Proportion of subjects with Adverse Events (AEs) [ Time Frame: Approximately Up to 4 years ]
    Grade 3 or higher per CTCAE v4 (Common Terminology Criteria for Adverse Events)

  • Proportion of subjects with Serious Adverse Events (SAEs) [ Time Frame: Approximately Up to 4 years ]
    Grade 3 or higher per CTCAE v4 ( Common Terminology Criteria for Adverse Events)

  • Proportion of Deaths [ Time Frame: Approximately Up to 4 years ]
  • Proportion of subjects with laboratory abnormalities [ Time Frame: Approximately Up to 4 years ]
  • Progression Free Survival (PFS) [ Time Frame: Approximately Up to 4 years ]

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 ]
  • Time of maximum observed serum concentration (Tmax) of BMS-986016 administered both alone and in combination with nivolumab [ Time Frame: Approximately 2.3 years ]
  • Trough observed serum concentration (Ctrough) of BMS-986016 administered both alone and in combination with nivolumab [ Time Frame: Approximately 2.3 years ]
  • 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 ]
  • 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 ]
  • 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 ]
  • Total body clearance (CLT) of BMS-986016 administered both alone and in combination with nivolumab [ Time Frame: Approximately 2.3 years ]
  • Volume of distribution at steady state (Vss) of BMS-986016 administered both alone and in combination with nivolumab [ Time Frame: Approximately 2.3 years ]
  • 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 ]
    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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • Efficacy as measured by tumor assessment (RECIST) [ Time Frame: Approximately 4 years ]
    Based on 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 ]
    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 ]
  • Best overall response (BOR) [ Time Frame: Approximately 4 years ]
  • Objective response rate (ORR) [ Time Frame: Approximately 4 years ]
  • Disease control rate (DCR) [ Time Frame: Approximately 4 years ]
  • Duration of response (DOR) [ Time Frame: Approximately 4 years ]
  • Progression-free survival (PFS) [ Time Frame: Approximately 4 years ]

Estimated Enrollment: 360
Study Start Date: October 2013
Estimated Study Completion Date: October 2019
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)
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: subjects with cervical, ovarian, bladder and CRC, head and neck, gastric and hepatocellular cancer naive to immuno-oncology agents; 1st line melanoma and 1st line/2nd line 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, except for subjects in 1st line cohorts.
  • ECOG performance status of 0 or 1
  • At least 1 lesion with measurable disease at baseline
  • Availability of an existing tumor biopsy sample (and consent to allow pre-treatment tumor biopsy)

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 #.

  Show 25 Study Locations
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: January 27, 2017

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 February 17, 2017