A Phase I Study of an Anti-KIR Antibody in Combination With an Anti-PD1 Antibody in Patients With Advanced Solid Tumors

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by Bristol-Myers Squibb
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT01714739
First received: October 24, 2012
Last updated: August 27, 2014
Last verified: August 2014

October 24, 2012
August 27, 2014
October 2012
September 2017   (final data collection date for primary outcome measure)
  • Safety and tolerability of BMS-986015 given in combination with BMS-936558 as measured by incidence of adverse events [ Time Frame: Approximately up to 27 months ] [ Designated as safety issue: Yes ]
  • Safety and tolerability of BMS-986015 given in combination with BMS-936558 as measured by incidence of clinical laboratory test abnormalities including hematology and serum chemistry, and thyroid panel abnormalities [ Time Frame: Approximately up to 27 months ] [ Designated as safety issue: Yes ]
Same as current
Complete list of historical versions of study NCT01714739 on ClinicalTrials.gov Archive Site
  • Anti-tumor activity will be based on Best overall response (BOR), Objective response rate (ORR), Duration of Response (DOR) and Progression-Free Survival Rate (PFSR) using Immune-related RECIST (irRECIST) and RECIST v1.1 [ Time Frame: Approximately up to 27 months ] [ Designated as safety issue: No ]

    Every 8 weeks during the Treatment Period (Cycle 1 Day 1 through Cycle 12 Day 56), and once during clinical follow-up

    RECIST = Response Evaluation Criteria In Solid Tumors

  • Maximum observed serum concentration (Cmax) of BMS-986015 derived from serum concentration versus time [ Time Frame: 13 time points up to 27 months ] [ Designated as safety issue: Yes ]
  • Time of maximum observed serum concentration (Tmax) of BMS-986015 derived from serum concentration versus time [ Time Frame: 13 time points up to 27 months ] [ Designated as safety issue: Yes ]
  • 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 [ Time Frame: 13 time points up to 27 months ] [ Designated as safety issue: Yes ]
  • 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 [ Time Frame: 13 time points up to 27 months ] [ Designated as safety issue: Yes ]
  • Trough observed serum concentration (Ctrough) of BMS-986015 derived from serum concentration versus time [ Time Frame: 13 time points up to 27 months ] [ Designated as safety issue: Yes ]
  • Area under the concentration-time curve in one dosing interval [AUC(TAU)] of BMS-986015 derived from serum concentration versus time [ Time Frame: 13 time points up to 27 months ] [ Designated as safety issue: Yes ]
  • Clearance (CL) of BMS-986015 derived from serum concentration versus time [ Time Frame: 13 time points up to 27 months ] [ Designated as safety issue: Yes ]
  • Volume of distribution at steady state (Vss) of BMS-986015 derived from serum concentration versus time [ Time Frame: 13 time points up to 27 months ] [ Designated as safety issue: Yes ]
  • Half-life (t1/2) of BMS-986015 derived from serum concentration versus time [ Time Frame: 13 time points up to 27 months ] [ Designated as safety issue: Yes ]
  • End of infusion of BMS-936558 derived from serum concentration versus time [ Time Frame: 9 time points up to 27 months ] [ Designated as safety issue: Yes ]
  • Trough observed concentration (Cmin) of BMS-936558 derived from serum concentration versus time [ Time Frame: 9 time points up to 27 months ] [ Designated as safety issue: Yes ]
  • Immunogenicity of BMS-986015 and BMS-936558 measured by occurrence of specific anti-drug antibodies to BMS-986015 and BMS-936558 [ Time Frame: Approximately up to 27 months ] [ Designated as safety issue: Yes ]
  • Measures of Tumor infiltrating lymphocyte(s) (TILs), Programmed Death Ligand-1 (PD-L1) and Human Leukocyte Antigen (HLA) Class I expression using immunohistochemistry [ Time Frame: Screening (Day -28 to -1) and Day 112 ] [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
A Phase I Study of an Anti-KIR Antibody in Combination With an Anti-PD1 Antibody in Patients With Advanced Solid Tumors
A Phase 1 Dose Escalation and Cohort Expansion Study of the Safety, Tolerability and Efficacy of Anti-KIR (Lirilumab) Administered in Combination With Anti-PD-1 (Nivolumab) in Patients With Advanced Solid Tumors

The purpose of this study is to assess the safety and tolerability of BMS-986015 given in combination with BMS-936558 and to identify dose limiting toxicities (DLTs) and the maximally tolerated dose (MTD) of the combination, in subjects with advanced (metastatic and/or unresectable) solid tumors.

Not Provided
Interventional
Phase 1
Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
CANCER,NOS
  • Drug: Lirilumab
    KIR = Killer-cell Immunoglobulin-like Receptors
    Other Names:
    • BMS-986015
    • IPH-2102
    • ANTI-KIR
  • Drug: Nivolumab
    Other Names:
    • BMS-936558
    • ANTI-PD1
  • Experimental: Arm 1: Dose Escalation (Lirilumab 0.1mg/kg+Nivolumab 3mg/kg)

    Lirilumab 0.1 mg/kg solution intravenously every 4 weeks for 8-96 weeks depending on response

    Nivolumab 3 mg/kg solution intravenously every 2 weeks for 8-96 weeks depending on response

    Interventions:
    • Drug: Lirilumab
    • Drug: Nivolumab
  • Experimental: Arm 2: Dose Escalation (Lirilumab 0.3mg/kg+Nivolumab 3mg/kg)

    Lirilumab 0.3 mg/kg solution intravenously every 4 weeks for 8-96 weeks depending on response

    Nivolumab 3 mg/kg solution intravenously every 2 weeks for 8-96 weeks depending on response

    Interventions:
    • Drug: Lirilumab
    • Drug: Nivolumab
  • Experimental: Arm 3: Dose Escalation (Lirilumab 1mg/kg+Nivolumab 3mg/kg)

    Lirilumab 1 mg/kg solution intravenously every 4 weeks for 8-96 weeks depending on response

    Nivolumab 3 mg/kg solution intravenously every 2 weeks for 8-96 weeks depending on response

    Interventions:
    • Drug: Lirilumab
    • Drug: Nivolumab
  • Experimental: Arm 4: Dose Escalation (Lirilumab 3mg/kg+Nivolumab 3mg/kg)

    Lirilumab 3 mg/kg solution intravenously every 4 weeks for 8-96 weeks depending on response

    Nivolumab 3 mg/kg solution intravenously every 2 weeks for 8-96 weeks depending on response

    Interventions:
    • Drug: Lirilumab
    • Drug: Nivolumab
  • Experimental: Arm 5: Various Solid Tumors

    Lirilumab 3 mg/kg solution intravenously every 4 weeks for 8-96 weeks depending on response

    Nivolumab 3 mg/kg solution intravenously every 2 weeks for 8-96 weeks depending on response

    Interventions:
    • Drug: Lirilumab
    • Drug: Nivolumab
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
162
September 2017
September 2017   (final data collection date for primary outcome measure)

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. Mandatory on-treatment biopsies for selected tumor types in cohort expansion phase
  • 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:

  • Prior therapy with an immune cell modulating antibody except for anti-Cytotoxic T Lymphocyte Antigen 4 (CTLA4)
  • 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)
Both
18 Years and older
No
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 #.
United States
 
NCT01714739
CA223-001
No
Bristol-Myers Squibb
Bristol-Myers Squibb
Not Provided
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
Bristol-Myers Squibb
August 2014

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