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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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01968109
Recruitment Status : Active, not recruiting
First Posted : October 23, 2013
Last Update Posted : March 29, 2024
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb

Study Description
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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.


Condition or disease Intervention/treatment Phase
Neoplasms by Site Biological: Relatlimab Biological: Nivolumab Biological: BMS-986213 Phase 1 Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1499 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (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
Actual Study Start Date : November 5, 2013
Estimated Primary Completion Date : September 10, 2024
Estimated Study Completion Date : September 10, 2024

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Relatlimab
Relatlimab (BMS-986016) specified dose on specified days
 Biological: Relatlimab
Other Names:
  • BMS-986016
  • Anti-LAG-3 (Anti-Lymphocyte Activation Gene-3)
Experimental: Relatlimab + Nivolumab
Relatlimab (BMS-986016) + Nivolumab (BMS-936558) specified dose on specified days
 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
Experimental: BMS-986213
Relatlimab (BMS-986016) + Nivolumab (BMS-936558)
 Biological: BMS-986213
Relatlimab + Nivolumab


Outcome Measures
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Primary Outcome Measures :
  1. Proportion of participants with Adverse Events (AEs) [ Time Frame: Approximately Up to 3 years ]
    Grade 3 or higher per CTCAE v4 (Common Terminology Criteria for Adverse Events)

  2. Proportion of participants 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)

  3. Proportion of Deaths [ Time Frame: Approximately Up to 3 years ]
  4. Proportion of participants with laboratory abnormalities in blood [ Time Frame: Approximately Up to 3 years ]
  5. Proportion of participants with laboratory abnormalities in blood serum [ Time Frame: Approximately Up to 3 years ]
  6. Proportion of participants with laboratory abnormalities in urine [ Time Frame: Approximately Up to 3 years ]
  7. Objective response rate (ORR) [ Time Frame: Approximately 3 years ]
  8. Disease control rate (DCR) [ Time Frame: Approximately 3 years ]
  9. Duration of response (DOR) [ Time Frame: Approximately 3 years ]
  10. Number of AEs in the Broad Scope MedDRA Anaphylactic Reaction SMQ [ Time Frame: Approximately 3 years ]
  11. Proportion of participants with AEs leading to discontinuation of treatment [ Time Frame: Approximately up to 3 years ]

Secondary Outcome Measures :
  1. Maximum observed serum concentration (Cmax) of BMS-986016 administered both alone and in combination with nivolumab [ Time Frame: Approximately 2.3 years ]
  2. Time of maximum observed serum concentration (Tmax) of BMS-986016 administered both alone and in combination with nivolumab [ Time Frame: Approximately 2.3 years ]
  3. Trough observed serum concentration (Ctrough) of BMS-986016 administered both alone and in combination with nivolumab [ Time Frame: Approximately 2.3 years ]
  4. 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 ]
  5. 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 ]
  6. Total body clearance (CLT) of BMS-986016 administered both alone and in combination with nivolumab [ Time Frame: Approximately 2.3 years ]
  7. Volume of distribution at steady state (Vss) of BMS-986016 administered both alone and in combination with nivolumab [ Time Frame: Approximately 2.3 years ]
  8. 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 ]
  9. 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 ]
  10. 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 ]
  11. 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 ]
  12. 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 ]
  13. 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 ]
  14. Immunogenicity measured by anti-drug antibody (ADA) for BMS-986016 (all participants) and nivolumab [ Time Frame: Approximately 2.3 years ]
  15. QTc interval from centrally read electrocardiograms (ECGs) [ Time Frame: Approximately 2.3 years ]
  16. Best overall response (BOR) [ Time Frame: Approximately 3 years ]
  17. ORR [ Time Frame: Approximately 3 years ]
  18. DCR [ Time Frame: Approximately 3 years ]
  19. Duration of response (DOR) [ Time Frame: Approximately 3 years ]
  20. Progression-free survival (PFS) rates [ Time Frame: Up to approximately 3 years ]
  21. Overall survival (OS) [ Time Frame: Approximately 2 years ]
  22. Number of AEs in the Narrow Scope MedDRA Anaphylactic Reaction SMQ [ Time Frame: Approximately 3 years ]

Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   12 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 participants 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

Other protocol defined inclusion/exclusion criteria could apply

Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01968109


Locations
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Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
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Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
More Information
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Additional Information:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT01968109    
Other Study ID Numbers: CA224-020
2023-508067-70 ( Registry Identifier: EU Trial Number )
First Posted: October 23, 2013    Key Record Dates
Last Update Posted: March 29, 2024
Last Verified: March 2024

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Neoplasms by Site
Neoplasms
Nivolumab
Relatlimab
 Antineoplastic Agents, Immunological
Antineoplastic Agents
Immune Checkpoint Inhibitors
Molecular Mechanisms of Pharmacological Action