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A Study of an Anti-KIR Antibody Lirilumab in Combination With an Anti-PD1 Antibody Nivolumab and Nivolumab Plus an Anti-CTLA-4 Ipilimumab Antibody in Patients With Advanced Solid Tumors

Sponsor
Bristol-Myers Squibb (Industry)
Overall Status
Completed
CT.gov ID
NCT01714739
Collaborator
(none)
337
Enrollment
30
Locations
4
Arms
86.2
Actual Duration (Months)
11.2
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

To assess the safety and tolerability and preliminary anti-tumor activity of lirilumab (BMS-986015) given in combination with nivolumab (BMS-936558) and to identify dose limiting toxicities (DLTs) and the maximally tolerated dose (MTD) of the combination. In addition, to assess the combinations of lirilumab and nivolumab or lirilumab and nivolumab plus ipilimumab (BMS-734016) in subjects with advanced (metastatic and/or unresectable) refractory solid tumors.

Condition or Disease Intervention/Treatment Phase
Phase 1/Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
337 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Care Provider, Investigator)
Primary Purpose:
Treatment
Official Title:
A Phase 1/2 Study of the Combination of Lirilumab (Anti-KIR) Plus Nivolumab (Anti-PD-1) or Lirilumab Plus Nivolumab and Ipilimumab in Advanced Refractory Solid Tumors
Actual Study Start Date :
Oct 7, 2012
Actual Primary Completion Date :
Dec 13, 2019
Actual Study Completion Date :
Dec 13, 2019

Arms and Interventions

Arm Intervention/Treatment
Experimental: Part 1

Dose Escalation and Initial Signal Detection in Multiple Solid Tumors - Nivolumab with Lirilumab

Drug: Lirilumab
Specified dose on specified days.
Other Names:
  • BMS-986015
  • IPH-2102
  • ANTI-KIR (Killer-cell Immunoglobulin-like Receptors)

    • Drug: Nivolumab
    Specified dose on specified days.
    Other Names:
  • BMS-936558
  • ANTI-PD1

    		•
    Experimental: Part 2 and 3: Cohort Expansion

    In platinum-refractory recurrent or metastatic SCCHN - Nivolumab with or without Lirilumab

    Drug: Lirilumab
    Specified dose on specified days.
    Other Names:
  • BMS-986015
  • IPH-2102
  • ANTI-KIR (Killer-cell Immunoglobulin-like Receptors)

    • Drug: Nivolumab
    Specified dose on specified days.
    Other Names:
  • BMS-936558
  • ANTI-PD1

    		•
    Experimental: Part 4: Cohort Expansion

    Additional Signal Detection in Solid Tumors - Nivolumab with Lirilumab (Study Part 4 Removed; No Subjects Enrolled)

    Drug: Lirilumab
    Specified dose on specified days.
    Other Names:
  • BMS-986015
  • IPH-2102
  • ANTI-KIR (Killer-cell Immunoglobulin-like Receptors)

    • Drug: Nivolumab
    Specified dose on specified days.
    Other Names:
  • BMS-936558
  • ANTI-PD1

    		•
    Experimental: Part 5 and 6

    Safety Lead-In and Additional Signal Detection in Solid Tumors -- Nivolumab Plus Ipilimumab with Lirilumab (Study Part 6 Removed; No Subjects Enrolled)

    Drug: Lirilumab
    Specified dose on specified days.
    Other Names:
  • BMS-986015
  • IPH-2102
  • ANTI-KIR (Killer-cell Immunoglobulin-like Receptors)

    • Drug: Nivolumab
    Specified dose on specified days.
    Other Names:
  • BMS-936558
  • ANTI-PD1

    • Drug: Ipilimumab
    Specified dose on specified days.
    Other Names:
  • BMS-734016
  • Anti-CTLA4

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Safety and tolerability of BMS-986015 given in combination with BMS-936558 or BMS-936558 plus BMS-734016 as measured by incidence of adverse events [Approximately 3 years]

    2. Safety and tolerability of BMS-986015 given in combination with BMS-936558 or BMS-936558 plus BMS-734016 as measured by incidence of clinical laboratory test abnormalities including hematology, serum chemistry, and thyroid panel abnormalities [Approximately 3 years]

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

    Secondary Outcome Measures

    1. Maximum observed serum concentration (Cmax) of BMS-986015 derived from serum concentration versus time [Approximately 27 months]

    2. Time of maximum observed serum concentration (Tmax) of BMS-986015 derived from serum concentration versus time [Approximately 27 months]

    3. Area under the plasma concentration-time curve from time zero to time of last quantifiable concentration [AUC(0-T)] of BMS-986015 derived from serum concentration versus time [Approximately 27 months]

    4. Area under the plasma concentration-time curve from time zero extrapolated to infinite time [AUC(INF)] of BMS-986015 derived from serum concentration versus time [Approximately 27 months]

    5. Trough observed serum concentration (Ctrough) of BMS-986015 derived from serum concentration versus time [Approximately 27 months]

    6. Area under the concentration-time curve in one dosing interval [AUC(TAU)] of BMS-986015 derived from serum concentration versus time [Approximately 27 months]

    7. Clearance (CL) of BMS-986015 derived from serum concentration versus time [Approximately 27 months]

    8. Volume of distribution at steady state (Vss) of BMS-986015 derived from serum concentration versus time [Approximately 27 months]

    9. Half-life (t1/2) of BMS-986015 derived from serum concentration versus time [Approximately 27 months]

    10. Anti-drug antibody (ADA) response to BMS-986015 in combination with BMS-936558 or BMS-734016 [Approximately 27 months]

    11. Overall survival (OS) [Approximately 3 years]

    12. Progression-Free Survival (PFS) [Approximately 3 years]

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

    Eligibility Criteria

    Criteria

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

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

    Inclusion Criteria:

    • During dose escalation, subjects with advanced solid tumors (except for primary CNS metastases) that have progressed following at least one standard regimen

    • During cohort expansion, subjects with various solid tumors that have received at least one and no more than 5 prior treatment regimens

    • Subjects must have measurable disease

    • Subject must consent to provide previously collected tumor tissue

    • Women and men ≥18 years of age with performance status of 0 or 1

    • At least 4 weeks since any previous treatment for cancer

    Exclusion Criteria:

    • Active or chronic autoimmune diseases

    • Uncontrolled or significant cardiovascular disease

    • Chronic hepatitis (except for subjects with hepatocellular carcinoma)

    • Active infection

    • Active Central nervous system (CNS) metastases

    • Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome((HIV/AIDS)

    • Positive test for Hepatitis B virus surface antigen or Hepatitis C antibody (except for subjects with hepatocellular carcinoma)

    Other protocol defined inclusion/exclusion criteria could apply

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Ucsf San Francisco California United States 94115
    2 Florida Cancer Affiliates - Ocala Ocala Florida United States 34471
    3 University Of Chicago Medical Center Chicago Illinois United States 60637
    4 Sidney Kimmel Comprehensive Cancer Center At Johns Hopkins Lutherville Maryland United States 21093
    5 Beth Israel Deaconess Med Ctr Boston Massachusetts United States 02215
    6 Dana Farber Cancer Institute Boston Massachusetts United States 02215
    7 Massachusetts General Hospital Boston Massachusetts United States 02215
    8 Memorial Sloan Kettering Cancer Center New York New York United States 10065
    9 The Ohio State University Wexner Medical Center Columbus Ohio United States 43210
    10 Providence Portland Med Ctr Portland Oregon United States 97213
    11 Thomas Jefferson University Hospital Philadelphia Pennsylvania United States 19107
    12 UPMC Eye and Ear Institute Pittsburgh Pennsylvania United States 15213
    13 West Cancer Center Germantown Tennessee United States 38138
    14 Texas Oncology-Central Austin Cancer Center Austin Texas United States 78731
    15 University Of Texas Medical Branch Of Galveston Galveston Texas United States 77555
    16 University Of Washington Seattle Washington United States 98195
    17 Juravinski Cancer Center Hamilton Ontario Canada L8V 5C2
    18 Princess Margaret Cancer Centre Toronto Ontario Canada M5G 2M9
    19 Local Institution Bordeaux France 33075
    20 Local Institution Lyon Cedex 08 France 69373
    21 Local Institution Nice Cedex 2 France 06189
    22 Local Institution Paris France 75005
    23 Institut Gustave Roussy Villejuif Cedex France 94805
    24 IRCCS Istituto Nazionale Tumori Milano Milano MI Italy 20133
    25 Local Institution Siena Italy 53100
    26 Local Institution Barcelona Spain 08035
    27 Local Institution Madrid Spain 28034
    28 Local Institution Madrid Spain 28050
    29 Kantonsspital Graubuenden Chur Switzerland 7000
    30 Centre Hospitalier Universitaire Vaudois Lausanne Switzerland 1011

    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:
    NCT01714739
    Other Study ID Numbers:
    • CA223-001
    First Posted:
    Oct 26, 2012
    Last Update Posted:
    Dec 14, 2020
    Last Verified:
    Dec 1, 2020
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Neoplasms
    Nivolumab
    Ipilimumab
    Immunoglobulins

    Study Results

    No Results Posted as of Dec 14, 2020