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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 May 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: May 15, 2017
Last verified: May 2017

September 25, 2013
May 15, 2017
October 14, 2013
May 6, 2018   (Final data collection date for primary outcome measure)
  • 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 ]
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) ]

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

AEs = Adverse events;

SAEs = Serious adverse events

Complete list of historical versions of study NCT01968109 on ClinicalTrials.gov Archive Site
  • 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 ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
    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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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 ]
    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 ]
  • 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) ]
Not Provided
Not Provided
 
Safety Study of Anti-LAG-3 With and Without Anti-PD-1 in the Treatment of Solid Tumors
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
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.
Not Provided
Interventional
Phase 1
Phase 2
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: No masking
Primary Purpose: Treatment
Neoplasms by Site
  • 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
  • Experimental: BMS-986016
    BMS-986016 specified dose on specified days
    Intervention: Biological: BMS-986016
  • Experimental: BMS-986016 + BMS-936558
    BMS-986016 + BMS-936558 specified dose on specified days
    Interventions:
    • Biological: BMS-986016
    • Biological: BMS-936558
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
360
October 11, 2019
May 6, 2018   (Final data collection date for primary outcome measure)

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
Sexes Eligible for Study: All
18 Years and older   (Adult, Senior)
No
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 #.
United States,   Austria,   Denmark,   Finland,   France,   Germany,   Italy,   Netherlands,   Norway,   Spain,   Switzerland,   United Kingdom
Japan
 
NCT01968109
CA224-020
2014-002605-38 ( EudraCT Number )
No
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Not Provided
Not Provided
Bristol-Myers Squibb
Bristol-Myers Squibb
Not Provided
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
Bristol-Myers Squibb
May 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP