A Phase I, Open Label, Dose Escalation and Expansion, Two- Part Study of SHP-2 Inhibitor BBP-398 to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Anti-cancer Activity in Chinese Subjects With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- LianBio LLC
- 入组人数
- 7
- 试验地点
- 2
- 主要终点
- Determination of anti-tumor activity of BBP-398
研究概览
简要总结
This is an open label, dose escalation and expansion, two-part Phase I study for SHP-2 inhibitor BBP-398 to evaluate the safety, tolerability, pharmacokinetics, determine MTD and/or RP2D, and preliminary anti- cancer activity in Chinese subjects with advanced solid tumors and in Chinese subjects with advanced or metastatic EGFR-mutant NSCLC.
详细描述
The Part A of this phase I trial is an abbreviated dose escalation study of BBP-398 following the USA mono dose escalation study (Study NAV- 1001, clinicaltrials.gov ID NCT04528836). The purpose of this part is to evaluate the safety, tolerability, pharmacokinetics, and preliminary anti-cancer activity in Chinese subjects with advanced solid tumors. The Part B of this study is to explore the safety, tolerability and efficacy of BBP-398 in Chinese subjects with advanced or metastatic EGFR- mutant NSCLC at MTD and/or RP2D. This Phase I study will provide supportive data to enable Chinese patients to join the combo dose escalation and expansion studies and/or other clinical trials of BBP-398.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •Patients must have the ability to understand and the willingness to sign a written informed consent document 2 Patients must be willing and able to comply with the scheduled visits, treatment plan, laboratory tests and other specified study procedures
- •Age ≥18, male or female 4.Dose escalation: locally advanced or metastatic solid tumors Dose expansion: Advanced or metastatic EGFR-mutant NSCLC
- •Patients must have measurable disease by RECIST v1.
- •Patients must have an ECOG performance status (PS) ≤2 7.Patients with a life expectancy of ≥12 weeks.
- •Patients must have adequate organ function
排除标准
- •Patients with a known additional malignancy that is progressing or requires active treatment
- •Patients who have previously received a SHP-2 inhibitor
- •Patients who are hypersensitivity to SHP-2 inhibitor or any ingredients
- •Treatment with any of the related anti-cancer therapies prior to the first dose of BBP-398 within the stated timeframes
- •Patients with known active Hepatitis B, Hepatitis C infection, or HIV infection.
- •Patients with any of the cardiac-related issues or findings
- •Patients with a history of CVA, myocardial infarction or unstable angina within the previous 6 months before starting therapy.
- •Patients with known central nervous system (CNS) tumors
- •Patients with known active CNS metastases and/or carcinomatous meningitis.
- •Patients with persisting toxicity related to prior therapy.
- •Patients who have undergone major surgery within 4 weeks prior to study enrollment.
- •Pregnant or breastfeeding female patients.
- •Patients with inability to swallow oral medications or with gastrointestinal illness that would preclude the absorption of an oral agent.
研究组 & 干预措施
Part A Dose Escalation and Part B Dose Expansion
Part A: Oral capsules taken in escalating levels to determine MTD/RP2D. Each treatment cycle will be 28 days in duration with BBP-398 administered, once daily (QD).
Part B: Oral capsules administered at MTD/RP2D defined dose. Each treatment cycle will be 28 days in duration with BBP-398 administered, once daily (QD)
干预措施: BBP-398 (Drug)
结局指标
主要结局
Determination of anti-tumor activity of BBP-398
时间窗: Completion of 1 Cycle (28 days)
Anti-tumor activity will be defined by objective response rate (ORR, complete response + partial response rate) and duration of response (DOR) according to RECIST v1.1
Determination of Maximum Tolerated Dose (MTD) of BBP-398
时间窗: Completion of 1 Cycle (28 days)
The MTD will be based on DLT
次要结局
- Part A:Maximum plasma concentration (Cmax) of BBP-398(Approximately 6 months)
- Part A: Terminal half-life (t1/2) of BBP-398(Approximately 6months)
- Part A: Area under the plasma concentration-time curve (AUC) of BBP-398(Approximately 6 months)
- Part A: Concentration of BBP-398 in urine(Approximately 6 months)
- Part A:Time to reach Cmax (Tmax) of BBP-398(Approximately 6 months)
- Part B: Concentration of BBP-398 in plasma(Approximately 6 months)