Study of Cabiralizumab in Patients With Pigmented Villonodular Synovitis / Diffuse Type Tenosynovial Giant Cell Tumor

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

Detailed Description
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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).

Official Title
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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)

Conditions
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Pigmented Villonodular Synovitis, Tenosynovial Giant Cell Tumor

Intervention / Treatment
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* Biological: FPA008


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase 1 FPA008 Dose Escalation<br>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<br>* FPA008 will be administered by IV infusion over approximately 30 minutes every 2 or 4 weeks<br>* Other names: Cabiralizumab;|
| Experimental: Phase 2 FPA008 Dose Expansion<br>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<br>* FPA008 will be administered by IV infusion over approximately 30 minutes every 2 or 4 weeks<br>* Other names: Cabiralizumab;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diffuse Type Tenosynovial Giant Cell Tumor (dt-TGCT)