Clinical trial NCT01714739: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: CANCER,NOS
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2012-10-26
Enrollment: 337
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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
* 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

Primary outcomes:
measure: Number of Participants With Adverse Events (AEs) - Parts 1, 2 and 5
timeFrame: From first dose to 150 days post last dose (up to an average of 51 weeks and a maximum of 2.5 years)
measure: Number of Participants With Serious Adverse Events (SAEs) - Parts 1, 2 and 5
timeFrame: From first dose to 150 days post last dose (up to an average of 51 weeks and a maximum of 2.5 years)
measure: Number of Participants With Adverse Events (AEs) Leading to Discontinuation - Parts 1, 2 and 5
timeFrame: From first dose to 150 days post last dose (up to an average of 51 weeks and a maximum of 2.5 years)
measure: The Number of Participant Deaths in the Study - Parts 1, 2 and 5
timeFrame: From first dose to 150 days post last dose (up to an average of 51 weeks and a maximum of 2.5 years)
measure: Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5
timeFrame: From first dose to 150 days post last dose (up to an average of 51 weeks and a maximum of 2.5 years)
measure: Objective Response Rate (ORR)
timeFrame: From first dose up to approximately 2.5 years
Secondary outcomes:
measure: Disease Control Rate (DCR) - Part 3
timeFrame: From first dose up to approximately 2.5 years
measure: Median Duration of Response (mDOR) - Parts 3 and 5
timeFrame: From first dose to the date of the first documented tumor progression as determined or death due to any cause, whichever occurs first. (Up to approximately 2.5 years)
measure: Median Time to Response (mTTR) - Part 3
timeFrame: From date of first dose of study medication to the date of the first documented objective response (up to approximately 2.5 years)
measure: The Number of Participants With >=50% or >=80% Tumor Reduction - Parts 3 and 5
timeFrame: From first dose until progressive disease (PD) or treatment discontinuation, whichever occurs earlier. (Up to approximately 2.5 years)
measure: Overall Survival (OS) - Part 3
timeFrame: From date of first dose of study medication to the date of death for any cause. (Up to approximately 2.5 years)
measure: Progression Free Survival (PFS) - Part 3
timeFrame: From first dose to the date of first objectively documented disease progression or death due to any cause, whichever occurs first. (Up to approximately 2.5 years)
measure: Progression Free Survival Rate (PFSR) at 6 Months - Part 3
timeFrame: At 6 months after first dose
measure: Number of Participants With Adverse Events (AEs) - Part 3
timeFrame: From first dose to 150 days post last dose (up to an average of 51 weeks and a maximum of 2.5 years)
measure: Number of Participants With Serious Adverse Events (SAEs) - Part 3
timeFrame: From first dose to 150 days post last dose (up to an average of 51 weeks and a maximum of 2.5 years)
measure: Number of Participants With Adverse Events (AEs) Leading to Discontinuation - Part 3
timeFrame: From first dose to 150 days post last dose (up to an average of 51 weeks and a maximum of 2.5 years)
measure: The Number of Participant Deaths in the Study - Part 3
timeFrame: From first dose to 150 days post last dose (up to an average of 51 weeks and a maximum of 2.5 years)
measure: Number of Participants With Clinical Laboratory Test Abnormalities - Part 3
timeFrame: From first dose to 150 days post last dose (up to an average of 51 weeks and a maximum of 2.5 years)
measure: Number of Participants With Anti-Drug Antibodies (ADA) - Parts 1, 2 and 5
timeFrame: From first dose to 100 days after last dose (up to approximately 126 weeks)
measure: The Number of Participants With PD-L1 Status at Pretreatment - Parts 1, 2 and 5
timeFrame: Pre-dose Day 1 (Cycles 1 ,3 ,5, 7, 9), Pre-dose Day 29 (Cycle 1, 2)
measure: Maximum Observed Plasma Concentration (Cmax) - Parts 1, 2 and 5
timeFrame: Pre-dose, end of infusion, 24, 168, and 336 hours post dose on day 1 cycle 1 and pre-dose on day 29 cycle 1. Pre-dose, end of infusion, 24 and 168 hours post dose on cycle 2 day 29.
measure: Area Under the Plasma Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration [AUC(0-T)] - Parts 1, 2 and 5
timeFrame: Pre-dose, end of infusion, 24, 168, and 336 hours post dose on day 1 cycle 1 and pre-dose on day 29 cycle 1. Pre-dose, end of infusion, 24 and 168 hours post dose on cycle 2 day 29.
measure: Area Under the Plasma Concentration-Time Curve in 1 Dosing Interval [AUC(TAU)] - Parts 1, 2 and 5
timeFrame: Pre-dose, end of infusion, 24, 168, and 336 hours post dose on day 1 cycle 1 and pre-dose on day 29 cycle 1. Pre-dose, end of infusion, 24 and 168 hours post dose on cycle 2 day 29.
measure: Time of Maximum Observed Concentration (Tmax) - Parts 1, 2 and 5
timeFrame: Pre-dose, end of infusion, 24, 168, and 336 hours post dose on day 1 cycle 1 and pre-dose on day 29 cycle 1. Pre-dose, end of infusion, 24 and 168 hours post dose on cycle 2 day 29.
measure: Half-life (T-HALF) - Parts 1, 2 and 5
timeFrame: Pre-dose, end of infusion, 24 and 168 hours post dose on cycle 2 day 29.
measure: Clearance Per Time (CLT) - Parts 1, 2 and 5
timeFrame: Pre-dose, end of infusion, 24 and 168 hours post dose on cycle 2 day 29.
measure: Trough Observed Concentration (Cmin, Also Known as CTAU) - Parts 1, 2 and 5
timeFrame: Pre-dose, end of infusion, 24, 168, and 336 hours post dose on day 1 cycle 1 and pre-dose on day 29 cycle 1. Pre-dose, end of infusion, 24 and 168 hours post dose on cycle 2 day 29.
measure: Area Under the Pasma Concentration-Time Curve From Time Zero Extrapolated to Infinite Time ([AUC(INF)] - Parts 1, 2 and 5
timeFrame: Pre-dose, end of infusion, 24, 168, and 336 hours post dose on day 1 cycle 1 and pre-dose on day 29 cycle 1. Pre-dose, end of infusion, 24 and 168 hours post dose on cycle 2 day 29.
measure: Apparent Volume of Distribution During Terminal Phase (Vz) - Parts 1, 2 and 5
timeFrame: Pre-dose, end of infusion, 24, 168, and 336 hours post dose on day 1 cycle 1 and pre-dose on day 29 cycle 1. Pre-dose, end of infusion, 24 and 168 hours post dose on cycle 2 day 29.
measure: End of Infusion Concentration (Ceoi) - Parts 1, 2 and 5 (Liri)
timeFrame: Pre-dose and end of infusion on cycle 1 day 1 and cycle 2 day 29.
measure: Ctrough - Parts 1, 2 and 5 (Liri)
timeFrame: Pre-dose on cycle 1 day 29 and Pre-dose and end of infusion on cycle 2 day 29.
measure: End of Infusion Concentration (Ceoi) - Parts 1, 2 and 5 (Nivo)
timeFrame: Pre-dose and end of infusion on cycle 1 day 1 and cycle 2 day 29.
measure: Ctrough - Parts 1, 2 and 5 (Nivo)
timeFrame: 336 hours post dose on cycle 1 day 1 (cycle 1 day 15) and pre-dose and end of infusion on cycle 2 day 29.
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: Ucsf
state: California
city: Ocala
country: United States
facility: Florida Cancer Affiliates - Ocala
state: Florida
city: Chicago
country: United States
facility: University Of Chicago Medical Center
state: Illinois
city: Lutherville
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center At Johns Hopkins
state: Maryland
city: Boston
country: United States
facility: Beth Israel Deaconess Med Ctr
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Columbus
country: United States
facility: The Ohio State University Wexner Medical Center
state: Ohio
city: Portland
country: United States
facility: Providence Portland Med Ctr
state: Oregon
city: Philadelphia
country: United States
facility: Thomas Jefferson University Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Eye and Ear Institute
state: Pennsylvania
city: Germantown
country: United States
facility: West Cancer Center
state: Tennessee
city: Austin
country: United States
facility: Texas Oncology-Central Austin Cancer Center
state: Texas
city: Galveston
country: United States
facility: University Of Texas Medical Branch Of Galveston
state: Texas
city: Seattle
country: United States
facility: University Of Washington
state: Washington
city: Hamilton
country: Canada
facility: Juravinski Cancer Center
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
city: Bordeaux
country: France
facility: Local Institution
city: Lyon Cedex 08
country: France
facility: Local Institution
city: Nice Cedex 2
country: France
facility: Local Institution
city: Paris
country: France
facility: Local Institution
city: Villejuif Cedex
country: France
facility: Institut Gustave Roussy
city: Milano
country: Italy
facility: IRCCS Istituto Nazionale Tumori Milano
state: MI
city: Siena
country: Italy
facility: Local Institution
city: Barcelona
country: Spain
facility: Local Institution
city: Madrid
country: Spain
facility: Local Institution - 0038
city: Madrid
country: Spain
facility: Local Institution
city: Chur
country: Switzerland
facility: Kantonsspital Graubuenden
city: Lausanne
country: Switzerland
facility: Centre Hospitalier Universitaire Vaudois
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: