A Multi-Center, Open-Label Phase 1b/2 Study of a Novel FGFR3 Inhibitor (B-701) Combined With Pembrolizumab in Subjects With Locally Advanced or Metastatic Urothelial Carcinoma Who Have Progressed Following Platinum-based Chemotherapy
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 28
- 试验地点
- 3
- 主要终点
- Number of Participants With Dose Limiting Toxicities Within a Period of 35 Days
研究概览
简要总结
This is a Phase 1b/2 multi-center, open-label study to establish the initial safety and to determine a recommended Phase 2 dose of B-701 in combination with pembrolizumab, and to determine safety, tolerability and efficacy of B-701 (vofatamab) plus pembrolizumab in the treatment of subjects with locally advanced or metastatic UCC, who have progressed following platinum-based chemotherapy and who have not received prior immune checkpoint inhibitor therapy.
详细描述
This is a Phase 1b/2 multi-center, open-label study to determine the safety, tolerability, and efficacy of B-701 (vofatamab) plus pembrolizumab in the treatment of subjects with locally advanced or metastatic UCC, who have progressed following platinum-based chemotherapy and who have not received prior immune checkpoint inhibitor or FGFR inhibitor-targeted therapy. The study consists of 2 parts: a Phase 1b lead-in phase enrolling 6 to 18 subjects and a Phase 2 dose expansion phase enrolling up to a total of 74 subjects.
Subjects who discontinue B-701 (vofatamab) may continue on study and receive pembrolizumab alone until disease progression, death, withdrawal of patient consent, or study termination. Subjects who discontinue pembrolizumab may continue on study and receive B-701 (vofatamab) alone until disease progression, death, withdrawal of patient consent, or study termination.
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
- •Have locally advanced (on TNM staging: T4b and any N, or any T and N2-3) or metastatic transitional cell carcinoma of the urothelium, including of the urinary bladder, urethra, ureter, and/or renal pelvis. The diagnosis must be histologically or cytologically confirmed.
- •Have progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.
- •Have available archival tumor or be willing to undergo diagnostic biopsy at screening. Sample must be of suitable quality and quantity to satisfy group assignment and biomarker endpoints.
- •Have measurable disease according to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1).
- •Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤
排除标准
- •Participants with a history of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on the Screening chest CT scan.
- •Prior therapy with an anti-programmed cell death 1 (PD-1) or anti-PD-Ligand 1 agent, or with an agent directed to another co-inhibitory T-cell receptor or FGFR inhibitor.
- •Patients with autoimmune disease or medical conditions that required systemic corticosteroids (> 10 mg/day prednisone or its equivalent) or other immunosuppressive medications or any other form of systemic immunosuppressive therapy within 7 days prior to the first dose of study treatment. Note: Replacement therapy (e.g. physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
- •Primary central nervous system (CNS) malignancy or CNS metastases.
- •History of clinically significant coagulation or platelet disorder in the past 12 months.
研究组 & 干预措施
B-701 (vofatamab)
B-701 (vofatamab, 25 mg/kg) will be administered via IV infusion on Cycle 0 Day 1 for a single 14-day cycle.
干预措施: B-701 (Drug)
B-701 (vofatamab) plus pembrolizumab
B-701 (vofatamab, 25 mg/kg [or the recommended Phase 2 dose if different than 25 mg/kg]) plus pembrolizumab (200 mg) will be administered by IV infusion on Cycle 1 Day 1 once every 3 weeks.
干预措施: B-701 (Drug)
B-701 (vofatamab) plus pembrolizumab
B-701 (vofatamab, 25 mg/kg [or the recommended Phase 2 dose if different than 25 mg/kg]) plus pembrolizumab (200 mg) will be administered by IV infusion on Cycle 1 Day 1 once every 3 weeks.
干预措施: Pembrolizumab (Drug)
结局指标
主要结局
Number of Participants With Dose Limiting Toxicities Within a Period of 35 Days
时间窗: 1 year
Number of Participants with Dose Limiting Toxicities within a period of 35 days will be analyzed reviewing the aggregate of adverse events (AEs) and serious adverse events (SAEs) by the B-701 program Safety Oversight Committee and will result in a recommended Phase 2 dose. Six subjects at a time are enrolled and observed for 35 days after the initial dose. If 2 or more subjects experience a DLT that dose will be declared intolerable and de-escalation of the dose will occur.
Number of Subjects Experiencing Adverse Events (AEs and SAEs)
时间窗: 2.5 years
Evaluate the safety and tolerability of B-701 (vofatamab) plus pembrolizumab in subjects with UCC as assessed by number of subjects experiencing adverse events (AEs and SAEs), physical examination findings, laboratory test results, and vital signs over time. This outcome is measured by a safety monitoring committee who regularly met and reviewed aggregate trends of reports AEs, lab ranges, physical exams etc. and determined if the drug was safe to continue.
Efficacy of B-701 (Vofatamab) Plus Pembrolizumab Measured by ORR
时间窗: 2 years
Evaluate the efficacy of B-701 (vofatamab) plus pembrolizumab in subjects with UCC as measured by objective response rate (ORR) by RECIST 1.1. ORR is defined as the percentage of subjects who have baseline measurable disease and who achieve a best response of either complete response (CR) or partial response (PR).
次要结局
- Assessment of Changes in Biomarkers Induced by B-701 (Vofatamab)(2.5 years)
- Efficacy of B-701 (Vofatamab) in Combination With Pembrolizumab as Measured by DOR(2 years)
- Efficacy of B-701 (Vofatamab) in Combination With Pembrolizumab as Measured by DCR(2 years)
- Efficacy of B-701 (Vofatamab) in Combination With Pembrolizumab as Measured by OS(2.5 years)
- Change in Subject Reported Quality of Life(2 years)
- Efficacy of B-701 (Vofatamab) in Combination With Pembrolizumab as Measured by PFS(2 years)