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)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 66
- 试验地点
- 12
- 主要终点
- The Incidence of Grade 3 and Grade 4 Adverse Events (AEs) and Defined as Dose-limiting Toxicities (DLTs) in Phase 1
研究概览
简要总结
This is a phase 1/2 single arm, open-label, safety, tolerability, and PK study of cabiralizumab in PVNS/dt-TGCT patients.
详细描述
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
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.
干预措施: FPA008 (Biological)
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.
干预措施: FPA008 (Biological)
结局指标
主要结局
The Incidence of Grade 3 and Grade 4 Adverse Events (AEs) and Defined as Dose-limiting Toxicities (DLTs) in Phase 1
时间窗: 52 weeks
Number of participants with grade 3 and grade 4 adverse events (AE) defined as dose limiting toxicities (DLTs) in Phase 1
The Incidence of Investigator-assessed, Confirmed Objective Responses (ORR) Per RECIST 1.1 (Phase 2)
时间窗: 52 weeks
Number of confirmed objective responses (ORR) as assessed by the investigator per RECIST 1.1 (Phase 2)
次要结局
- PK Parameters of Cabiralizumab: Area Under Concentration-time Curve (AUC)(52 weeks)
- Maximum Serum Concentration (Cmax).(52 weeks)
- Duration of Response Per RECIST 1.1 in Phase 2(52 weeks)
- Pharmacokinetic Clearance (CL).(52 weeks)
- The Incidence of Clinical Laboratory Abnormalities.(52 weeks)
- Minimum Serum Concentration (Cmin).(52 weeks)
- The Incidence of AEs.(52 weeks)
- The Incidence of ECG Abnormalities.(52 weeks)