An Open-Label, Multicenter, First-in-Human, Dose-Escalation and Dose-Expansion, Phase 1/2 Study of BBI-825 and BBI-825 in Combination With Select Targeted Therapies in Subjects With Locally Advanced or Metastatic Solid Tumors With Resistance Gene Amplifications
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 19
- 试验地点
- 5
- 主要终点
- Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D) of BBI-825
研究概览
简要总结
BBI-825 is a potent, selective, oral, small molecule inhibitor of ribonucleotide reductase (RNR). This is a first-in-human, open-label, non-randomized, 3-part, Phase 1/2 study to determine the safety profile and identify the maximum tolerated dose and recommended Phase 2 dose of BBI-825 administered as a single agent and in combination with select targeted therapies.
详细描述
BBI-825 will be administered orally (PO) twice daily (BID) to subjects with 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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 99 Years（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,
- •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
- •Prior exposure to a selective RNR inhibitor (Note: Prior exposure to chemotherapies with nonselective RNR inhibitory activity e.g., gemcitabine is permitted),
- •Receipt of any approved or considered standard of care anticancer drug(s) or biological product(s) within 4 weeks or 5 half-lives,
- •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,
- •Concurrent use of strong inhibitors or inducers of CYP3A, CYP2C8, CYP2C9, or CYP2C19,
- •Other exclusion criteria per study protocol.
研究组 & 干预措施
Single Agent Dose Escalation
Single agent BBI-825, administered orally, twice daily, in 28-day cycles
干预措施: BBI-825 (Drug)
结局指标
主要结局
Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D) of 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-825 will be determined.
Frequency and severity of treatment emergent adverse events (TEAEs) of 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.
次要结局
- Time to Cmax (Tmax) of 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-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-825(Start of Cycle 1 until Day 1 of last treatment cycle (each cycle is 28 days))
- Trough observed plasma concentration (Ctrough) of BBI-825(Start of Cycle 1 until Day 1 of last treatment cycle (each cycle is 28 days))
- Anti-tumor activity of BBI-825 as determined by RECISTv1.1(Start of Cycle 1 until Day 1 of last treatment cycle (each cycle is 28 days))