Study of Cabiralizumab in Patients With Pigmented Villonodular Synovitis / Diffuse Type Tenosynovial Giant Cell Tumor (FPA008-002)

A Phase 1/2 Study of Cabiralizumab, an Anti-CSF1 Receptor Antibody, in Patients With Pigmented Villonodular Synovitis (PVNS)/ Diffuse Type Tenosynovial Giant Cell Tumor (Dt-TGCT)

This is a phase 1/2 single arm, open-label, safety, tolerability, and PK study of cabiralizumab in PVNS/dt-TGCT patients.

Study Overview

• Status: Completed
• Conditions: Tenosynovial Giant Cell Tumor; Pigmented Villonodular Synovitis
• Intervention / Treatment: Biological: FPA008

Detailed Description

A Phase 1/2 study was an open-label, dose escalation and dose expansion study designed to evaluate the pharmacokinetics, pharmacodynamics, safety and preliminary efficacy of cabiralizumab, a CSF1-R monoclonal antibody, inpatients with unresectable diffuse tenosynovial giant cell tumors (TGCT).

• Study Type: Interventional
• Enrollment (Actual): 66
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• France
  • Bordeaux, France, 33076
    • Institut Bergonie- CRLCC de Bordeaux et du Sud-Ouest
  • Lyon, France, 69008
    • Centre Leon Berard
• Korea, Republic of
  • Jongno-gu
    • Seoul, Jongno-gu, Korea, Republic of, 110-744
      • Seoul National University Hospital
• Netherlands
  • Leiden, Netherlands, 2333 ZA
    • Leiden University Medical Center
• Poland
  • Warsaw, Poland, 02-781
    • Klinika Nowotworow Tkanek Miekkich, Kosci i Czerniakow, Centrum Onkologii-Instytut im. M. Sklodowskiej-Curie
• United Kingdom
  • Birmingham, United Kingdom, B15 2TH
    • University Hospitals Birmingham NHS Foundation Trust
  • Oxford, United Kingdom, OX3 7LE
    • Oxford University Hospital NHS Trust
• United States
  • California
    • Los Angeles, California, United States, 90048
      • Cedars-Sinai Medical Center
    • Santa Monica, California, United States, 90403
      • Sarcoma Oncology Research Center LLC
    • Stanford, California, United States, 94301-5821
      • Stanford Medicine
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber Cancer Institute
  • Texas
    • Houston, Texas, United States, 77030
      • The University of Texas, MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Histologically confirmed diagnosis of inoperable PVNS/ dt-TGCT or potentially resectable tumor that would result in unacceptable functional loss or morbidity as determined by a qualified surgeon or multi-disciplinary tumor board (must be documented in the CRF during screening)
• Measurable PVNS/dt-TGCT by RECIST 1.1 on MRI
• ECOG performance status <1

Exclusion Criteria:

• Prior therapy with an anti-CSF1R antibody
• Prior therapy with PLX3397 unless discontinued for intolerance (i.e., non-progression on prior kinase inhibitor)
• Liver function tests (including ALT, AST, and total bilirubin), outside of the range of local laboratory normal at Screening
• Inadequate organ or bone marrow function
• History of congestive heart failure or myocardial infarction <1 year prior to first study dose administration
• Significant abnormalities on ECG at Screening
• Contraindications to MRI and use of intravenous gadolinium-based contrast agents
• Creatine Kinase ≥ 1.5x the upper limit of normal
• Positive test for latent TB at Screening (Quantiferon test)
• Active known or suspected autoimmune disease

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 1 FPA008 Dose Escalation; IV infusion; safety data will be reviewed prior to dose escalation decision. Dose escalation will complete when recommended dose (RD) is determined. RD will be the maximum tolerated dose or lower dose that provide adequate PK exposure and biologic activity with tolerability.	Biological: FPA008; FPA008 will be administered by IV infusion over approximately 30 minutes every 2 or 4 weeks; Other Names: Cabiralizumab
Experimental: Phase 2 FPA008 Dose Expansion; IV infusion; once MTD and/or RD has been determined in Phase 1, expansion cohorts of approximately 30 patients (each cohort) with PVNS or dt-TGCT will be enrolled to characterize clinical activity and safety profile of the RD. Treatment is planned to continue for up to 24 weeks or 56 weeks.	Biological: FPA008; FPA008 will be administered by IV infusion over approximately 30 minutes every 2 or 4 weeks; Other Names: Cabiralizumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Incidence of Grade 3 and Grade 4 Adverse Events (AEs) and Defined as Dose-limiting Toxicities (DLTs) in Phase 1	Number of participants with grade 3 and grade 4 adverse events (AE) defined as dose limiting toxicities (DLTs) in Phase 1	52 weeks
The Incidence of Investigator-assessed, Confirmed Objective Responses (ORR) Per RECIST 1.1 (Phase 2)	Number of confirmed objective responses (ORR) as assessed by the investigator per RECIST 1.1 (Phase 2)	52 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PK Parameters of Cabiralizumab: Area Under Concentration-time Curve (AUC)	Area under serum concentration-time curve (AUC) for cabiralizumab as a PK parameter	52 weeks
Maximum Serum Concentration (Cmax).	Composite PK parameters of cabiralizumab: Maximum observed serum concentration	52 weeks
Minimum Serum Concentration (Cmin).	Composite PK parameters of cabiralizumab: minimum serum concentration (Cmin).	52 weeks
Pharmacokinetic Clearance (CL).	Composite PK parameters of cabiralizumab: clearance (CL)	52 weeks
The Incidence of AEs.	treatment-emergent adverse events (TEAEs) by incidence for the Safety Population. Patients with at lease 1 TEAE.	52 weeks
The Incidence of Clinical Laboratory Abnormalities.	The number of patients with a clinical laboratory that is outside the normal range at some time point during the study	52 weeks
The Incidence of ECG Abnormalities.	The number of patients who had a change in their ECG that were clinically significant	52 weeks
Duration of Response Per RECIST 1.1 in Phase 2	The length of response per RECIST 1.1 from the time of first response to progression or going off study in Phase 2	52 weeks

Collaborators and Investigators

• Sponsor: Five Prime Therapeutics, Inc.
• Investigators: Study Director: Medical Lead, Five Prime Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2015
• Primary Completion (Actual): April 30, 2020
• Study Completion (Actual): April 30, 2020

Study Registration Dates

• First Submitted: June 1, 2015
• First Submitted That Met QC Criteria: June 10, 2015
• First Posted (Estimate): June 15, 2015

Study Record Updates

• Last Update Posted (Actual): August 31, 2021
• Last Update Submitted That Met QC Criteria: August 4, 2021
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: Diffuse Type Tenosynovial Giant Cell Tumor (dt-TGCT)
• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Joint Diseases; Musculoskeletal Diseases; Muscular Diseases; Neoplasms, Connective Tissue; Tendinopathy; Synovitis; Giant Cell Tumors; Giant Cell Tumor of Tendon Sheath; Synovitis, Pigmented Villonodular
• Other Study ID Numbers: FPA008-002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No