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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

Sponsor
Bristol-Myers Squibb (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT01968109
Collaborator
(none)
1,499
Enrollment
53
Locations
3
Arms
121.8
Anticipated Duration (Months)
28.3
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

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
  • Biological: Relatlimab
  • Biological: Nivolumab
  • Biological: BMS-986213
 Phase 1/Phase 2

Study Design

Study Type:
Interventional
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 :
Nov 5, 2013
Anticipated Primary Completion Date :
Sep 26, 2022
Anticipated Study Completion Date :
Dec 31, 2023

Arms and Interventions

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

    Primary Outcome Measures

    1. Proportion of participants with Adverse Events (AEs) [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) [Approximately Up to 3 years]

      Grade 3 or higher per CTCAE v4 ( Common Terminology Criteria for Adverse Events)

    3. Proportion of Deaths [Approximately Up to 3 years]

    4. Proportion of participants with laboratory abnormalities in blood [Approximately Up to 3 years]

    5. Proportion of participants with laboratory abnormalities in blood serum [Approximately Up to 3 years]

    6. Proportion of participants with laboratory abnormalities in urine [Approximately Up to 3 years]

    7. Objective response rate (ORR) [Approximately 3 years]

    8. Disease control rate (DCR) [Approximately 3 years]

    9. Duration of response (DOR) [Approximately 3 years]

    10. Number of AEs in the Broad Scope MedDRA Anaphylactic Reaction SMQ [Approximately 3 years]

    11. Proportion of participants with AEs leading to discontinuation of treatment [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 [Approximately 2.3 years]

    2. Time of maximum observed serum concentration (Tmax) of BMS-986016 administered both alone and in combination with nivolumab [Approximately 2.3 years]

    3. Trough observed serum concentration (Ctrough) of BMS-986016 administered both alone and in combination with nivolumab [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 [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 [Approximately 2.3 years]

    6. Total body clearance (CLT) of BMS-986016 administered both alone and in combination with nivolumab [Approximately 2.3 years]

    7. Volume of distribution at steady state (Vss) of BMS-986016 administered both alone and in combination with nivolumab [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 [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 [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 [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 [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 [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 [Approximately 2.3 years]

    14. Immunogenicity measured by anti-drug antibody (ADA) for BMS-986016 (all participants) and nivolumab [Approximately 2.3 years]

    15. QTc interval from centrally read electrocardiograms (ECGs) [Approximately 2.3 years]

    16. Best overall response (BOR) [Approximately 3 years]

    17. ORR [Approximately 3 years]

    18. DCR [Approximately 3 years]

    19. Duration of response (DOR) [Approximately 3 years]

    20. Progression-free survival (PFS) rates [Up to approximately 3 years]

    21. Overall survival (OS) [Approximately 2 years]

    22. Number of AEs in the Narrow Scope MedDRA Anaphylactic Reaction SMQ [Approximately 3 years]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    12 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Locations

    Site City State Country Postal Code
    1 UCSD Moores Cancer Center La Jolla California United States 92093-0698
    2 University Of Colorado Aurora Colorado United States 80045
    3 H Lee Moffitt Cancer Center and Research Institute Tampa Florida United States 33612
    4 University Of Chicago Medical Center Chicago Illinois United States 60637
    5 Advocate Health and Hospitals Corporation Park Ridge Illinois United States 60068
    6 Sidney Kimmel Comprehensive Cancer Center At Johns Hopkins Baltimore Maryland United States 21287
    7 Dana-Farber Cancer Institute Boston Massachusetts United States 02215
    8 Karmanos Cancer Institute Detroit Michigan United States 48201
    9 Mayo Clinic - PPDS Rochester Minnesota United States 55905-0001
    10 Washington University School Of Medicine Saint Louis Missouri United States 63110
    11 Memorial Sloan Kettering Nassau New York New York United States 10065
    12 Providence Portland Med Ctr Portland Oregon United States 97213
    13 Lehigh Valley Hospital and Health Network Allentown Pennsylvania United States 18103
    14 UPMC Eye and Ear Institute Pittsburgh Pennsylvania United States 15232-1305
    15 Baylor Sammons Cancer Center Dallas Texas United States 75246
    16 Md Anderson Can Cnt Houston Texas United States 77030-4009
    17 University Of Washington Cancer Care Alliance Seattle Washington United States 98109
    18 Melanoma Institute Australia North Sydney New South Wales Australia 2060
    19 Gallipoli Medical Research Foundation Greenslopes Queensland Australia 4120
    20 Tasman Oncology Research Pty Ltd Southport Queensland Australia 4215
    21 Peter MacCallum Cancer Centre Melbourne Victoria Australia 3000
    22 Linear Clinical Research Ltd Nedlands Western Australia Australia 6009
    23 Local Institution Wien Austria 1090
    24 Local Institution Toronto Ontario Canada M5G 2M9
    25 CHU de Quebec - Universite Laval Quebec Canada G1R 2J6
    26 Local Institution Copenhagen Denmark 2100
    27 Local Institution Herlev Denmark 2730
    28 Local Institution Helsinki Finland 00290
    29 Local Institution Marseille Cedex 5 France 13385
    30 Local Institution Nantes Cedex 01 France 44093
    31 Local Institution Pierre Benite Cedex France 69495
    32 Local Institution Toulouse Cedex 9 France 31059
    33 Local Institution Villejuif France 94805
    34 Local Institution Essen Germany 45122
    35 Local Institution Heilbronn Germany 74078
    36 Local Institution Wuerzburg Germany 97080
    37 Istituto Europeo Di Oncologia Milano Italy 20141
    38 Istituto Nazionale Tumori Fondazione Pascale Napoli Italy 80131
    39 Istituto Oncologico Veneto - I.R.C.C.S. Padova Italy 35128
    40 Local Institution Nagoya-shi Aichi Japan 4668560
    41 Local Institution Sapporo-shi Hokkaido Japan 0608543
    42 Local Institution Sunto-gun Shizuoka Japan 4118777
    43 Local Institution Chuo-ku Tokyo Japan 1040045
    44 Antoni Van Leeuwenhoek Ziekenhuis Amsterdam Netherlands 1066 CX
    45 Local Institution Oslo Norway 0379
    46 H. Univ. Vall dHebron Barcelona Spain 08035
    47 Hospital Universitario Virgen De La Victoria Malaga Spain 29010
    48 Clinica Universidad de Navarra Pamplona Spain 31008
    49 Local Institution Lausanne Switzerland 1011
    50 Local Institution Zuerich Switzerland 8091
    51 University College Hospital London Greater London United Kingdom NW1 2PG
    52 Royal Marsden Nhs Foundation Trust London Greater London United Kingdom SW3 6JJ
    53 Christie Hospital Nhs Trust Manchester United Kingdom M20 4BX

    Sponsors and Collaborators

    • Bristol-Myers Squibb

    Investigators

    • Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Bristol-Myers Squibb
    ClinicalTrials.gov Identifier:
    NCT01968109
    Other Study ID Numbers:
    • CA224-020
    • 2014-002605-38
    First Posted:
    Oct 23, 2013
    Last Update Posted:
    Feb 11, 2022
    Last Verified:
    Feb 1, 2022
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Neoplasms by Site
    Nivolumab

    Study Results

    No Results Posted as of Feb 11, 2022