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Trial record 2 of 2 for:    Anti-LAG-3 Monoclonal Antibody (BMS-986016) Anti-PD-1 Monoclonal Antibody (Nivolumab, BMS-936558) | Advanced Solid Tumors

An Investigational Immuno-therapy Study to Assess the Safety, Tolerability and Effectiveness of Anti-LAG-3 With and Without Anti-PD-1 in the Treatment of Solid Tumors

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ClinicalTrials.gov Identifier: NCT01968109
Recruitment Status : Recruiting
First Posted : October 23, 2013
Last Update Posted : June 6, 2019
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb

Tracking Information
First Submitted Date  ICMJE September 25, 2013
First Posted Date  ICMJE October 23, 2013
Last Update Posted Date June 6, 2019
Actual Study Start Date  ICMJE October 14, 2013
Estimated Primary Completion Date December 31, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 4, 2019)
  • Proportion of subjects with Adverse Events (AEs) [ Time Frame: Approximately Up to 3 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 3 years ]
    Grade 3 or higher per CTCAE v4 ( Common Terminology Criteria for Adverse Events)
  • Proportion of Deaths [ Time Frame: Approximately Up to 3 years ]
  • Proportion of subjects with laboratory abnormalities [ Time Frame: Approximately Up to 3 years ]
  • Objective response rate (ORR) [ Time Frame: Approximately 3 years ]
  • Disease control rate (DCR) [ Time Frame: Approximately 3 years ]
  • Duration of response (DOR) [ Time Frame: Approximately 3 years ]
  • Proportion of participants with AEs meeting acute safety criteria [ Time Frame: Approximately 3 years ]
  • Proportion of subjects with AEs leading to discontinuation of treatment [ Time Frame: Approximately up to 3 years ]
Original Primary Outcome Measures  ICMJE
 (submitted: October 18, 2013)
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
Change History Complete list of historical versions of study NCT01968109 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: April 27, 2018)
  • 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 ]
  • 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 area under the concentration-time curve (AUC) accumulation observed (T-HALFeff AUC) 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 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 ]
  • Immunogenicity measured by anti-drug antibody (ADA) for BMS-986016 (all subjects) and nivolumab [ Time Frame: Approximately 2.3 years ]
  • QTc interval from centrally read electrocardiograms (ECGs) [ Time Frame: Approximately 2.3 years ]
  • Best overall response (BOR) [ Time Frame: Approximately 3 years ]
  • ORR [ Time Frame: Approximately 3 years ]
  • DCR [ Time Frame: Approximately 3 years ]
  • Duration of response (DOR) [ Time Frame: Approximately 3 years ]
  • Progression-free survival (PFS) [ Time Frame: Approximately 3 years ]
  • Overall survival (OS) [ Time Frame: Approximately 2 years ]
Original Secondary Outcome Measures  ICMJE
 (submitted: October 18, 2013)
  • 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) ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE An Investigational Immuno-therapy Study to Assess the Safety, Tolerability and Effectiveness of Anti-LAG-3 With and Without Anti-PD-1 in the Treatment of Solid Tumors
Official Title  ICMJE 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
Brief Summary

The purpose of the study is to assess the safety, tolerability and effectiveness of experimental medication BMS-986016 administered alone and in combination with nivolumab in patients with solid tumors that have spread and/or cannot be removed by surgery.

The following tumor types are included in this study:

Non-Small Cell Lung Cancer (NSCLC), gastric cancer, hepatocellular carcinoma, renal cell carcinoma, bladder cancer, squamous cell carcinoma of the head and neck, and melanoma, that have NOT previously been treated with immunotherapy. NSCLC and melanoma that HAVE previously been treated with immunotherapy.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Neoplasms by Site
Intervention  ICMJE
  • Biological: Relatlimab
    Other Names:
    • BMS-986016
    • Anti-LAG-3 (Anti-Lymphocyte Activation Gene-3)
  • Biological: Nivolumab
    Other Names:
    • Anti-PD-1 (Anti-Programmed-Death-1)
    • BMS-936558
  • Biological: BMS-986213
    Relatlimab + Nivolumab
Study Arms  ICMJE
  • Experimental: Relatlimab
    Relatlimab (BMS-986016) specified dose on specified days
    Intervention: Biological: Relatlimab
  • Experimental: Relatlimab + Nivolumab
    Relatlimab (BMS-986016) + Nivolumab (BMS-936558) specified dose on specified days
    Interventions:
    • Biological: Relatlimab
    • Biological: Nivolumab
  • Experimental: BMS-986213
    Relatlimab (BMS-986016) + Nivolumab (BMS-936558)
    Intervention: Biological: BMS-986213
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 4, 2019)
2000
Original Estimated Enrollment  ICMJE
 (submitted: October 18, 2013)
168
Estimated Study Completion Date  ICMJE December 31, 2023
Estimated Primary Completion Date December 31, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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

Inclusion Criteria:

  • For Dose escalation: subjects with cervical, ovarian, bladder and colorectal cancer (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, and CRC
  • Progressed, or been intolerant to, at least one standard treatment regimen, except for subjects in 1st line cohorts.
  • ECOG performance status between 0 and 2
  • 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 12 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
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 #.
Listed Location Countries  ICMJE Australia,   Austria,   Canada,   Denmark,   Finland,   France,   Germany,   Italy,   Japan,   Netherlands,   Norway,   Spain,   Switzerland,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01968109
Other Study ID Numbers  ICMJE CA224-020
2014-002605-38 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Bristol-Myers Squibb
Study Sponsor  ICMJE Bristol-Myers Squibb
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
PRS Account Bristol-Myers Squibb
Verification Date June 2019

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