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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

NCT01968109

Description:

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.

Related Conditions:
  • Bladder Carcinoma
  • Cervical Carcinoma
  • Gastric Carcinoma
  • Hepatocellular Carcinoma
  • Malignant Head and Neck Neoplasm
  • Melanoma
  • Non-Small Cell Lung Carcinoma
  • Ovarian Carcinoma
  • Renal Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: 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: 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

Clinical Trial IDs

  • ORG STUDY ID: CA224-020
  • SECONDARY ID: 2014-002605-38
  • NCT ID: NCT01968109

Conditions

  • Neoplasms by Site

Interventions

DrugSynonymsArms
RelatlimabBMS-986016, Anti-LAG-3 (Anti-Lymphocyte Activation Gene-3)Relatlimab
NivolumabAnti-PD-1 (Anti-Programmed-Death-1), BMS-936558Relatlimab + Nivolumab
BMS-986213BMS-986213

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
RelatlimabExperimentalRelatlimab (BMS-986016) specified dose on specified days
  • Relatlimab
Relatlimab + NivolumabExperimentalRelatlimab (BMS-986016) + Nivolumab (BMS-936558) specified dose on specified days
  • Relatlimab
  • Nivolumab
BMS-986213ExperimentalRelatlimab (BMS-986016) + Nivolumab (BMS-936558)
  • BMS-986213

Eligibility 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 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:12 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Proportion of subjects with Adverse Events (AEs)
Time Frame:Approximately Up to 3 years
Safety Issue:
Description:Grade 3 or higher per CTCAE v4 (Common Terminology Criteria for Adverse Events)

Secondary Outcome Measures

Measure:Maximum observed serum concentration (Cmax) of BMS-986016 administered both alone and in combination with nivolumab
Time Frame:Approximately 2.3 years
Safety Issue:
Description:
Measure:Time of maximum observed serum concentration (Tmax) of BMS-986016 administered both alone and in combination with nivolumab
Time Frame:Approximately 2.3 years
Safety Issue:
Description:
Measure:Trough observed serum concentration (Ctrough) of BMS-986016 administered both alone and in combination with nivolumab
Time Frame:Approximately 2.3 years
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:
Measure:Total body clearance (CLT) of BMS-986016 administered both alone and in combination with nivolumab
Time Frame:Approximately 2.3 years
Safety Issue:
Description:
Measure:Volume of distribution at steady state (Vss) of BMS-986016 administered both alone and in combination with nivolumab
Time Frame:Approximately 2.3 years
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:
Measure:Immunogenicity measured by anti-drug antibody (ADA) for BMS-986016 (all subjects) and nivolumab
Time Frame:Approximately 2.3 years
Safety Issue:
Description:
Measure:QTc interval from centrally read electrocardiograms (ECGs)
Time Frame:Approximately 2.3 years
Safety Issue:
Description:
Measure:Best overall response (BOR)
Time Frame:Approximately 3 years
Safety Issue:
Description:
Measure:ORR
Time Frame:Approximately 3 years
Safety Issue:
Description:
Measure:DCR
Time Frame:Approximately 3 years
Safety Issue:
Description:
Measure:Duration of response (DOR)
Time Frame:Approximately 3 years
Safety Issue:
Description:
Measure:Progression-free survival (PFS)
Time Frame:Approximately 3 years
Safety Issue:
Description:
Measure:Overall survival (OS)
Time Frame:Approximately 2 years
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Bristol-Myers Squibb

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