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

Five Prime Therapeutics

Status and phase: Completed; Phase 2; Phase 1

Conditions: Tenosynovial Giant Cell Tumor; Pigmented Villonodular Synovitis

Treatments: Biological: FPA008

Study type: Interventional

Funder types: Industry

Identifiers

NCT02471716

FPA008-002

Details and patient eligibility

About

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

Full 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).

Enrollment: 66 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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66 participants in 2 patient groups

Phase 1 FPA008 Dose Escalation

Experimental group

Description:

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.

Treatment:

Biological: FPA008

Phase 2 FPA008 Dose Expansion

Experimental group

Description:

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.

Treatment:

Biological: FPA008