Study of Cabiralizumab in Combination With Nivolumab in Patients With Selected Advanced Cancers

NCT02526017 | Completed Phase 1 Results DMC

• 1 other identifier: FPA008-003
• Study Type: interventional
• Target: 313
• Locations: 1 country
• Sites: 39

Brief Summary

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

Conditions

Advanced Solid Tumors; Head and Neck Cancer; Pancreatic Cancer; Ovarian Cancer; Renal Cell Carcinoma; Malignant Glioma; Non-small Cell Lung Cancer

Outcome Measures

Primary Outcomes (5)

• Safety: Number of Participants With Grade 3 or Grade 4 Adverse Events (AEs) and Laboratory Abnormalities Defined as Dose Limiting Toxicities (DLT) (Phase 1a)

  A DLT was defined as a study drug-related ≥ Grade 3 AE (using National Cancer Institute Common Terminology Criteria for Adverse Events v 4.03) occurring during the first 28-days, excluding Grade 3 tumor flare (defined as local pain, irritation, or rash localized at sites of known or suspected tumor), rash, immune-related adverse event (irAE) that resolved to ≤ Grade 1 by 14 days or a transient (resolving within 6 hours of onset) Grade 3 infusion-related AE. Any recurrence of Grade 3 rash, irAE or infusion-related AE was considered a DLT. The protocol was amended such that in the absence of clinical symptoms and other accompanying changes in bilirubin or alanine aminotransferase (ALT), serum elevation of aspartate aminotransferase (AST)/ALT \> 12 × upper limit of normal (ULN) and ≤ 20 × ULN that lasted for \< 7 days and serum elevation of creatine kinase (CK) and/or lactate dehydrogenase (LDH) \> 15 × ULN and ≤ 20 × ULN that lasted for \< 7 days were not considered DLTs.

  28 days

• Recommended Dose (RD) of Cabiralizumab in Combination With Nivolumab (Phase 1a)

  Using both the incidence of dose limiting toxicities (first 28 days on therapy) as well as overall tolerability and toxicities observed beyond 28 days, the RD was chosen as 4 mg/kg of cabiralizumab + 3 mg/kg nivolumab every 2 weeks to be the dose used in the Phase 1b (dose expansion). No maximum tolerated dose was identified.

  28 days

• Safety: Number of Participants With Adverse Events and Serious Adverse Events (Phase 1a and 1b)

  An AE is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation, patient-administered study drug and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (such as an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. A Serious Adverse Event (SAE) is any untoward medical occurrence that at any dose: * Resulted in death; * Was life-threatening; * Required inpatient hospitalization or causes prolongation of existing hospitalization; * Resulted in persistent or significant disability/incapacity; * Was a congenital anomaly/birth defect; * Was an important medical event that may jeopardize the patient or may require intervention (e.g., medical, surgical) to prevent one of the other serious outcomes listed in the definition above.

  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.

• Safety: Number of Participants With Treatment Discontinuations, Modifications, or Interruptions Due to Adverse Events (Phase 1b)

  Safety: In the Phase 1b only, the incidence of treatment discontinuations, modifications, and interruptions due to adverse events.

  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.

• Efficacy: Objective Response Rate - Investigator Assessment (Phase 1b)

  Objective response rate (ORR) is defined as the percentage of participants with confirmed responses of either complete response (CR) or partial response (PR). Response was evaluated using Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1 by investigator review. Complete Response: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial Response: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

  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 (9)

• Efficacy: Overall Survival (Phase 1b)

  From first dose of study drug up to the end of study; maximum time on study in Phase 1b was 35.9 months.

• Efficacy: Overall Survival (OS) at One Year (Phase 1b)

  52 weeks

• Efficacy: Duration of Response (Phase 1b)

  From first dose of study drug up to the end of study; maximum time on study in Phase 1b was 35.9 months.

• Efficacy: Progression Free Survival (Phase 1b)

  From first dose of study drug up to the end of study; maximum time on study in phase 1b was 35.9 months.

• Efficacy: Objective Response Rate - Central Review Assessment (Phase 1b)

  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.

Study Arms (3)

Phase 1a Monotherapy Dose Escalation

EXPERIMENTAL

Cabiralizumab administered at 2 mg/kg every 2 weeks (Q2W), 4 mg/kg Q2W and 6 mg/kg Q2W in participants with any solid tumor.

Biological: Cabiralizumab

Phase 1a Combination Therapy Dose Escalation

EXPERIMENTAL

Nivolumab 3 mg/kg Q2W + cabiralizumab at the following doses: 1 mg/kg, 2 mg/kg, 4 mg/kg, and 6 mg/kg Q2W. Also nivolumab 3 mg/kg + cabiralizumab 4 mg/kg every 3 weeks (Q3W). Participants with any solid tumor.

Biological: Cabiralizumab; Biological: Nivolumab

Phase 1b Combination Therapy Dose Expansion

EXPERIMENTAL

The expansion phase would use the recommended dose determined in Phase 1a: cabiralizumab 4 mg/kg + nivolumab 3 mg/kg Q2W. Participants are enrolled for the following advanced cancer types: non-small cell lung cancer (anti-programmed cell death 1 \[PD1\] targeted drug naïve), non-small cell lung cancer (prior treatment with anti-PD-1), pancreatic cancer, ovarian cancer, renal cell cancer, glioblastoma, and melanoma.

Biological: Cabiralizumab; Biological: Nivolumab

Interventions

Cabiralizumab BIOLOGICAL

Solution for IV administration

Also known as: Anti-colony stimulating factor-1 receptor (Anti-CSF-1R), FPA008

Phase 1a Combination Therapy Dose Escalation; Phase 1a Monotherapy Dose Escalation; Phase 1b Combination Therapy Dose Expansion

Nivolumab BIOLOGICAL

Solution for IV administration

Also known as: OPDIVO®, MDX-1106, BMS-936558

Phase 1a Combination Therapy Dose Escalation; Phase 1b Combination Therapy Dose Expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Five Prime Therapeutics, Inc.: lead
• Bristol-Myers Squibb: collaborator

Study Sites (39)

Scottsdale Healthcare Hospitals DBA Honor Health

Scottsdale, Arizona, 85258, United States

Location

Moores UC San Diego Cancer Center

La Jolla, California, 92093, United States

Location

Norris Comprehensive Cancer Center, University of Southern California

Los Angeles, California, 90033, United States

Location

Cedars-Sinai Medical Center, Samuel Oschin Comprehensive Cancer Center

Los Angeles, California, 90048, United States

Location

UC Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

Location

University of California, San Francisco

San Francisco, California, 94143, United States

Location

Sarcoma Oncology Research Center

Santa Monica, California, 90403, United States

Location

UCLA Hematology/Oncology- Santa Monica

Santa Monica, California, 90404, United States

Location

Mount Sinai Comprehensive Cancer Center

Miami Beach, Florida, 33140, United States

Location

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, 33612, United States

Location

Emory University Hospital

Atlanta, Georgia, 30322, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

University of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

Indiana University Health Hospital

Indianapolis, Indiana, 46202, United States

Location

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

Location

Norton Cancer Institute, Norton Healthcare Pavilion

Louisville, Kentucky, 40202, United States

Location

Johns Hopkins Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, 21287, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

Allina Health, Virginia Piper Cancer Institute

Minneapolis, Minnesota, 55407, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

Memorial Sloan Kettering

New York, New York, 10065, United States

Location

The Christ Hospital

Cincinnati, Ohio, 45219, United States

Location

Providence Portland Medical Center

Portland, Oregon, 97213, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, 19107, United States

Location

University of Pittsburgh Cancer Institute, William M. Cooper Ambulatory Pavilion of the Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

Hollings Cancer Center, Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Henry-Joyce Cancer Clinic, Vanderbilt-Ingram Cancer Center,

Nashville, Tennessee, 37232, United States

Location

Baylor Charles A. Sammons Cancer Center, Baylor University Medical Center

Dallas, Texas, 75246, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Mischer Neuroscience Associates, The University of Texas Health Science Center at Houston

Houston, Texas, 77030, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Cancer Therapy & Research Center, University of Texas Health Science Center at San Antonio

San Antonio, Texas, 78229, United States

Location

South Texas Accelerated Research Therapeutics, LLC

San Antonio, Texas, 78229, United States

Location

Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

Seattle Cancer Care Alliance

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Head and Neck Neoplasms; Pancreatic Neoplasms; Ovarian Neoplasms; Carcinoma, Renal Cell; Glioma; Carcinoma, Non-Small-Cell Lung

Interventions

cabiralizumab; Nivolumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Digestive System Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Gonadal Disorders; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Kidney Neoplasms; Urologic Neoplasms; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

Inclusion of multiple tumor types and several dose levels in monotherapy and combination with nivolumab limits the ability to accurately evaluate the incidence of off-target effects adverse events.

Results Point of Contact

• Title: Helen Collins, Chief Medical Officer
• Organization: Five Prime Therapeutics

helen.collins@fiveprime.com

650-745-9633

Study Officials

• Medical Lead

  Five Prime Therapeutics, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 13, 2015
• First Posted: August 18, 2015
• Study Start: September 8, 2015
• Primary Completion: November 18, 2019
• Study Completion: November 18, 2019
• Last Updated: March 9, 2022
• Results First Posted: March 9, 2022

Record last verified: 2022-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (39)