Clinical trial NCT02526017: Study of Cabiralizumab in Combination With Nivolumab in Patients With Selected Advanced Cancers
Official title: A Phase 1a/1b Study of Cabiralizumab in Combination With Nivolumab in Patients With Selected Advanced Cancers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Solid Tumors
Head and Neck Cancer
Pancreatic Cancer
Ovarian Cancer
Renal Cell Carcinoma
Malignant Glioma
Non-small Cell Lung Cancer
Lead sponsor: Five Prime Therapeutics, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Bristol-Myers Squibb
First posted: 2015-08-18
Enrollment: 313
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: Phase 1a/1b does-escalation study of cabiralizumab alone and with nivolumab in advanced solid tumors.

Detailed description: This is a phase 1a/b single-arm, open-label study to evaluate safety, tolerability, pharmacokinetics (PK), and clinical benefit of cabiralizumab in combination with nivolumab in patients with selected advanced cancers.

Eligibility criteria: Inclusion Criteria:

* Patients must have at least one measurable lesion at baseline by computed tomography (CT) or magnetic resonance imaging (MRI) as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria.
* Patients must have had progressive disease on, after, or refused, appropriate approved therapy for their tumor type.
* Patients must have histologically or cytologically confirmed solid tumor that is locally recurrent or metastatic and has progressed following standard treatment or is not appropriate for standard treatment
* Understand and sign an Institutional review board/Independent ethics committee (IRB/IEC)-approved informed consent form (ICF) prior to any study-specific evaluation
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Willing and able to comply with all study procedures

Exclusion Criteria:

* Current or history of clinically significant muscle disorders (e.g., myositis), recent unresolved muscle injury, or any condition known to elevate serum creatine kinase (CK) levels
* Decreased cardiac function with New York Heart Association (NYHA) \> Class 2
* Uncontrolled or significant heart disorder such as unstable angina
* Significant abnormalities on electrocardiogram (ECG) at screening. Fridericia's correction formula for QT interval (QTcF) \> 450 msec for males or \> 470 msec for females at screening
* History of anti-drug antibodies, severe allergic, anaphylactic, or other infusion-related reaction to a previous biologic agent
* Positive test for latent tuberculosis (TB) at screening (Quantiferon test) or evidence of active TB
* Patients with abnormal serum chemistry values, which in the opinion of the Investigator is considered to be clinically significant, will be excluded from the study
* Lack of peripheral venous or central venous access or any condition that would interfere with drug administration or collection of study samples
* Any uncontrolled medical condition or psychiatric disorder which, in the opinion of the Investigator, would pose a risk to patient safety or interfere with study participation or interpretation of individual patient results
* Pregnant or breastfeeding
* Current unresolved infection or history of chronic, active, clinically significant infection (viral, bacterial, fungal, or other) which, in the opinion of the Investigator, would preclude the patient from exposure to a biologic agent or pose a risk to patient safety
* Prior exposure to any colony stimulating factor 1 receptor (CSF1R) pathway inhibitors

Primary outcomes:
measure: Safety: Number of Participants With Grade 3 or Grade 4 Adverse Events (AEs) and Laboratory Abnormalities Defined as Dose Limiting Toxicities (DLT) (Phase 1a)
timeFrame: 28 days
measure: Recommended Dose (RD) of Cabiralizumab in Combination With Nivolumab (Phase 1a)
timeFrame: 28 days
measure: Safety: Number of Participants With Adverse Events and Serious Adverse Events (Phase 1a and 1b)
timeFrame: From first dose of study drug up to 100 days after last dose. Median (range) duration of exposure was 6 (2-32) weeks in the monotherapy cohorts and 8 (2-108) weeks for cabiralizumab and 8 (2-156) weeks for nivolumab in the combination groups.
measure: Safety: Number of Participants With Treatment Discontinuations, Modifications, or Interruptions Due to Adverse Events (Phase 1b)
timeFrame: From first dose of study drug up to last dose; median (range) duration of exposure was 8 (2-108) weeks for cabiralizumab and 8 (2-156) weeks for nivolumab.
measure: Efficacy: Objective Response Rate - Investigator Assessment (Phase 1b)
timeFrame: Tumor response was assessed every 8 weeks from first dose for the first 12 months and then every 12 weeks thereafter until end of treatment; maximum duration of treatment was 156 weeks.
Secondary outcomes:
measure: Efficacy: Overall Survival (Phase 1b)
timeFrame: From first dose of study drug up to the end of study; maximum time on study in Phase 1b was 35.9 months.
measure: Efficacy: Overall Survival (OS) at One Year (Phase 1b)
timeFrame: 52 weeks
measure: Efficacy: Duration of Response (Phase 1b)
timeFrame: From first dose of study drug up to the end of study; maximum time on study in Phase 1b was 35.9 months.
measure: Efficacy: Progression Free Survival (Phase 1b)
timeFrame: From first dose of study drug up to the end of study; maximum time on study in phase 1b was 35.9 months.
measure: Efficacy: Objective Response Rate - Central Review Assessment (Phase 1b)
timeFrame: Tumor response was assessed every 8 weeks from first dose for the first 12 months and then every 12 weeks thereafter until end of treatment; maximum duration of treatment was 156 weeks.
measure: Pharmacokinetics (PK) of Cabiralizumab: Area Under the Concentration Curve From Time Zero to Time of Last Quantifiable Concentration (AUC0-t) Normalized by Dose (Phase 1a and 1b)
timeFrame: Cycles 1 and 8, Day 1 predose, and at 0.25, 4, 24, 72, 168, and 336 hours after the end of infusion.
measure: PK of Cabiralizumab: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin)
timeFrame: Cycles 1 and 8, Day 1 predose, and at 0.25, 4, 24, 72, 168, and 336 hours after the end of infusion.
measure: Immunogenicity of Cabiralizumab: Number of Participants With Anti-Cabiralizumab Antibodies (Phase 1a and 1b)
timeFrame: Blood samples were collected before the infusion on Cycles 1 (Baseline), 2, 3, 4, 5, 9, 13, and 21, and at 28 days and 100 days after the end of treatment
measure: Immunogenicity of Nivolumab: Number of Participants With Anti-Nivolumab Antibodies (Phase 1a and 1b)
timeFrame: Blood samples were collected before the infusion on Cycles 1 (Baseline), 2, 3, 4, 5, 9, 13, and 21, and at 28 days and 100 days after the end of treatment
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Scottsdale Healthcare Hospitals DBA Honor Health
state: Arizona
city: La Jolla
country: United States
facility: Moores UC San Diego Cancer Center
state: California
city: Los Angeles
country: United States
facility: Norris Comprehensive Cancer Center, University of Southern California
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center, Samuel Oschin Comprehensive Cancer Center
state: California
city: Sacramento
country: United States
facility: UC Davis Comprehensive Cancer Center
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Santa Monica
country: United States
facility: Sarcoma Oncology Research Center
state: California
city: Santa Monica
country: United States
facility: UCLA Hematology/Oncology- Santa Monica
state: California
city: Miami Beach
country: United States
facility: Mount Sinai Comprehensive Cancer Center
state: Florida
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center and Research Institute
state: Florida
city: Atlanta
country: United States
facility: Emory University Hospital
state: Georgia
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University Health Hospital
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: Louisville
country: United States
facility: Norton Cancer Institute, Norton Healthcare Pavilion
state: Kentucky
city: Baltimore
country: United States
facility: Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
state: Maryland
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Minneapolis
country: United States
facility: Allina Health, Virginia Piper Cancer Institute
state: Minnesota
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering
state: New York
city: Cincinnati
country: United States
facility: The Christ Hospital
state: Ohio
city: Portland
country: United States
facility: Providence Portland Medical Center
state: Oregon
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Cancer Institute, William M. Cooper Ambulatory Pavilion of the Hillman Cancer Center
state: Pennsylvania
city: Charleston
country: United States
facility: Hollings Cancer Center, Medical University of South Carolina
state: South Carolina
city: Nashville
country: United States
facility: Henry-Joyce Cancer Clinic, Vanderbilt-Ingram Cancer Center,
state: Tennessee
city: Dallas
country: United States
facility: Baylor Charles A. Sammons Cancer Center, Baylor University Medical Center
state: Texas
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: Mischer Neuroscience Associates, The University of Texas Health Science Center at Houston
state: Texas
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: Cancer Therapy & Research Center, University of Texas Health Science Center at San Antonio
state: Texas
city: San Antonio
country: United States
facility: South Texas Accelerated Research Therapeutics, LLC
state: Texas
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute
state: Utah
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance
state: Washington
Study officials:
affiliation: Five Prime Therapeutics, Inc.
name: Medical Lead
role: STUDY_DIRECTOR
References: