A Phase 1/2, Open Label, Multicenter Study to Investigate the Safety, Pharmacokinetics, and Efficacy of TAS0728, an Oral Covalent Binding Inhibitor of HER2, in Subjects With Advanced Solid Tumors With HER2 or HER3 Abnormalities
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 19
- 试验地点
- 8
- 主要终点
- Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] (Phase 1 and 2)
研究概览
简要总结
This is a First-in-Human (FIH), 2-part, Phase 1/2, open-label, multicenter study design to evaluate the safety, tolerability, PK, pharmacodynamics, PGx, and efficacy of TAS0728. This study consists of Phase 1 and Phase 2 components in subjects with advanced solid tumors with HER2 or HER3 overexpression, amplification, or mutation who have progressed despite standard therapy or for which no standard therapy exists, particularly urothelial cancer, biliary tract cancer, metastatic breast cancer, non-small cell lung cancer and colorectal cancer.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or females with an age ≥ 18 years.
- •Subjects with histological- or cytological-confirmed, advanced cancer, who have progressed on (or not been able to tolerate) standard therapy or for whom no standard anticancer therapy exists
- •For Phase 1, only subjects HER2 or HER3 molecular/genetic alterations will be enrolled.
- •For Phase 2a, subjects with one of the following tumor types will be enrolled:
- •i. Urothelial cancer with HER2 or HER3 mutation ii. Biliary tract cancer with HER2 or HER3 mutation iii. Breast cancer with HER2 or HER3 mutation iv. Breast cancer with HER2 amplification or overexpression v. NSCLC with HER2 or HER3 mutation vi. CRC with HER2 mutation or amplification vii. Other tumors with HER2 mutation/amplification/overexpression or HER3 mutation (gastric/GEJ, endometrial).
- •At least 1 measurable lesion for solid tumor
- •Is able to take medications orally (e.g., no feeding tube).
- •Able to agree to and sign informed consent and to comply with the protocol
- •Has adequate organ function
排除标准
- •Has a serious illness or medical condition(s)
- •Has received treatment with any proscribed treatments within specified time frames prior to study drug administration
- •Impaired cardiac function or clinically significant cardiac disease
研究组 & 干预措施
TAS0728
Group 1: Urothelial cancer with HER2 or HER3 mutation Group 2: Biliary tract cancer with HER2 or HER3 mutation Group 3: Breast cancer with HER2 or HER3 mutation Group 4: Breast cancer with HER2 amplification or overexpression as per American Society of Clinical Oncology - College of American Pathologists (ASCO-CAP) 2013 guidelines Group 5: Non-small cell lung cancer (NSCLC) with HER2 or HER3 mutation Group 6: Colorectal cancer (CRC) with HER2 mutation or amplification Group 7: Other tumors with HER2 or HER3 mutation, amplification, or overexpression (eg, gastric or gastroesophageal junction (GEJ), endometrial)
干预措施: TAS0728 (Drug)
结局指标
主要结局
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] (Phase 1 and 2)
时间窗: Safety monitoring will begin at the informed consent obtained and continue up to 30 days after the last dose of TAS0728 or until new antitumor therapy, whichever is earlier.
Number of patients experiencing Dose Limiting Toxicity graded according to CTCAE Version 4.03, observed in the Cycle 1 in order to meet the objective of assessment of the MTD of TAS0728.
时间窗: 21-day cycles
Objective Response Rate using Response Evaluation Criteria in Solid Tumors 1.1 (RECIST) (Phase2)
时间窗: 3 years
次要结局
- Duration of response (phase 1 and 2)(3 years)
- Maximum Plasma Concentration (Cmax) after administration of TAS0728 (Phase 1)(21 days in Cycle 1)
- Overall survival (phase 1 and 2)(3 years)
- Area under the plasma drug concentration-time curve (AUC) after administration of TAS0728 (Phase 1)(21 days in Cycle 1)
- Disease Control Rate using RECIST 1.1 (phase 1 and 2)(3 years)
- Progression free survival (phase 1 and 2)(3 years)