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
  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 2017
Estimated Primary Completion Date: September 2017 (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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01714739

Contacts
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 #.

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    410-502-5352      
United States, Massachusetts
Dana-Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Contact: F. Stephen Hodi, Site 0006    617-726-4292      
Dana Faber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Contact: F. Stephen Hodi, Site 0007    617-632-9285      
Dana Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Contact: F. Stephen Hodi, Site 0001    617-582-7545      
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: August 27, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Additional relevant MeSH terms:
Neoplasms

ClinicalTrials.gov processed this record on October 02, 2014