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.
Verified March 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: March 25, 2014
Last verified: March 2014
  Purpose

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.


Condition Intervention Phase
CANCER,NOS
Drug: Lirilumab
Drug: Nivolumab
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 162
Study Start Date: October 2012
Estimated Study Completion Date: September 2015
Estimated Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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 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

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 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

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 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

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 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

Drug: Lirilumab
KIR = Killer-cell Immunoglobulin-like Receptors
Other Names:
  • BMS-986015
  • IPH-2102
  • ANTI-KIR
Drug: Nivolumab
Other Names:
  • BMS-936558
  • ANTI-PD1

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01714739

Contacts
Contact: For participation information at a USA site use a phone number below. For site information outside the USA please email: Clinical.Trials@bms.com
Contact: First line of email MUST contain NCT# & Site#. Only trial sites that are recruiting have contact information at this time.

Locations
United States, Illinois
University Of Chicago Medical Center Recruiting
Chicago, Illinois, United States, 60637
Contact: Thomas F Gajewski, Site 0005    773-834-1942      
United States, Maryland
Sidney Kimmel Comprehensive Cancer Center At Johns Hopkins Recruiting
Lutherville, Maryland, United States, 21093
Contact: William Sharfman, Site 0002    410-955-0009      
United States, Massachusetts
Local Institution Not yet recruiting
Boston, Massachusetts, United States, 02215
Contact: Site 0006         
Local Institution Not yet recruiting
Boston, Massachusetts, United States, 02215
Contact: Site 0007         
Dana Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Contact: F. Stephen Hodi, Site 0001    617-632-4715      
United States, New York
Memorial Sloan Kettering Cancer Ctr Recruiting
New York, New York, United States, 10065
Contact: Neil Segal, Site 0003    646-888-3359      
United States, Oregon
Providence Portland Med Ctr Recruiting
Portland, Oregon, United States, 97213
Contact: Rachel Sanborn, Site 0004    503-215-2604      
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
No publications provided

Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT01714739     History of Changes
Other Study ID Numbers: CA223-001
Study First Received: October 24, 2012
Last Updated: March 25, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

ClinicalTrials.gov processed this record on April 17, 2014