An Open-Label, Multicenter, First-in-Human, Dose-Escalation and Dose-Expansion, Phase 1/2 Study of BBI-355 and BBI-355 in Combination With Select Targeted Therapies in Subjects With Locally Advanced or Metastatic Solid Tumors With Oncogene Amplifications
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 85
- 试验地点
- 30
- 主要终点
- Frequency and severity of treatment emergent adverse events (TEAEs) of BBI-355 as a single agent and in combination with each of the following agents: erlotinib, futibatinib, or BBI-825
研究概览
简要总结
BBI-355 is an oral, potent, selective checkpoint kinase 1 (or CHK1) small molecule inhibitor in development as an ecDNA (extrachromosomal DNA) directed therapy (ecDTx). BBI-825 is an oral, potent, selective ribonucleotide reductase (or RNR) small molecule inhibitor. This is a first-in-human, open-label, 2-part, Phase 1/2 study to determine the safety profile and identify the maximum tolerated dose and recommended Phase 2 dose of BBI-355 administered as a single agent or in combination with BBI-825 or other select therapies.
详细描述
BBI-355 and BBI-825 are administered orally in various dosing schedules to subjects with locally advanced or metastatic non-resectable solid tumors harboring oncogene amplifications, whose disease has progressed despite all standard therapies or for whom no further standard or clinically acceptable therapy exists.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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
- •Locally advanced or metastatic non-resectable solid tumors, whose disease has progressed despite all standard therapies or for whom no further standard or clinically acceptable therapy exists,
- •Evidence of oncogene amplification,
- •Availability of FFPE tumor tissue, archival or newly obtained,
- •Measurable disease as defined by RECIST Version 1.1,
- •Adequate hematologic function,
- •Adequate hepatic and renal function,
- •Eastern Cooperative Oncology Group performance status (ECOG PS) 0 or 1,
- •Other inclusion criteria per study protocol.
排除标准
- •Single agent arm: Prior exposure to CHK1 or WEE1 inhibitors,
- •BBI-355 combination with BBI-825 arm: Prior exposure to combination therapy of any RNR inhibitor plus CHK1/2 inhibitor,
- •Hematologic malignancies,
- •Primary CNS malignancy, leptomeningeal disease, or symptomatic active CNS metastases, with exceptions per study protocol,
- •Prior or concurrent malignancies, with exceptions per study protocol,
- •History of HBV, HCV, or HIV infection,
- •Clinically significant cardiac condition,
- •Active or history of interstitial lung disease (ILD) or pneumonitis, or history of ILD or pneumonitis requiring steroids or other immunosuppressive medications,
- •QTcF > 470 msec,
- •Prior organ allograft transplantations or allogeneic peripheral blood stem cell/bone marrow transplantation,
- •Other exclusion criteria per study protocol.
研究组 & 干预措施
Dose Escalation in Combination with FGFR Inhibitor
Combination therapy of BBI-355 and FGFR1-4 inhibitor futibatinib, administered orally in 28-day cycles.
干预措施: BBI-355 (Drug)
Single Agent Dose Expansion
Single agent BBI-355, administered orally in 28-day cycles
干预措施: BBI-355 (Drug)
Dose Escalation in Combination with RNR Inhibitor
Combination therapy of BBI-355 and RNR Inhibitor BBI-825, administered orally in 28-day cycles.
干预措施: BBI-355 (Drug)
Dose Escalation in Combination with RNR Inhibitor
Combination therapy of BBI-355 and RNR Inhibitor BBI-825, administered orally in 28-day cycles.
干预措施: BBI-825 (Drug)
Dose Escalation in Combination with EGFR Inhibitor
Combination therapy of BBI-355 and EGFR inhibitor erlotinib, administered orally in 28-day cycles.
干预措施: Erlotinib (Drug)
Single Agent Dose Escalation
Single agent BBI-355, administered orally in 28-day cycles
干预措施: BBI-355 (Drug)
Dose Escalation in Combination with FGFR Inhibitor
Combination therapy of BBI-355 and FGFR1-4 inhibitor futibatinib, administered orally in 28-day cycles.
干预措施: Futibatinib (Drug)
Dose Escalation in Combination with EGFR Inhibitor
Combination therapy of BBI-355 and EGFR inhibitor erlotinib, administered orally in 28-day cycles.
干预措施: BBI-355 (Drug)
结局指标
主要结局
Frequency and severity of treatment emergent adverse events (TEAEs) of BBI-355 as a single agent and in combination with each of the following agents: erlotinib, futibatinib, or BBI-825
时间窗: Start of Cycle 1 until 30 days following last dose (each cycle is 28 days)
TEAEs will be assessed and severity assigned by using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0.
Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D) of BBI-355 as a single agent and in combination with erlotinib, futibatinib, or BBI-825
时间窗: Start of Cycle 1 until 30 days following last dose (each cycle is 28 days)
The MTD and/or RP2D of BBI-355 as a single agent and in combination with erlotinib, futibatinib, or BBI-825 will be determined.
次要结局
- Time to Cmax (Tmax) of BBI-355, erlotinib, futibatinib, and BBI-825(Start of Cycle 1 until Day 1 of last treatment cycle (each cycle is 28 days))
- Maximum observed plasma concentration (Cmax) of BBI-355, erlotinib, futibatinib, and BBI-825(Start of Cycle 1 until Day 1 of last treatment cycle (each cycle is 28 days))
- Trough observed plasma concentration (Ctrough) of BBI-355, erlotinib, futibatinib, and BBI-825(Start of Cycle 1 until Day 1 of last treatment cycle (each cycle is 28 days))
- Area under the concentration time curve (AUC) of BBI-355, erlotinib, futibatinib, and BBI-825(Start of Cycle 1 until Day 1 of last treatment cycle (each cycle is 28 days))
- Anti-tumor activity of BBI-355 as a single agent and in combination with erlotinib, futibatinib, or BBI-825(1-2 years: Start of Cycle 1 until documented disease progression or death (each cycle is 28 days))