Phase 1 Study of BPI-442096 in Advanced Solid Tumor Patients
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 230
- 试验地点
- 5
- 主要终点
- Determine the recommended Phase II dose (RP2D)
研究概览
简要总结
A first-in-human study to evaluate the safety, tolerability and maximum tolerated dose (MTD) and establish the recommended phase 2 dose (RP2D) of BPI-442096, a SHP2 inhibitor, in patients with advanced solid tumors.
详细描述
The first-in-human (FIH) study of BPI-442096 will be an open-label, non-randomized, Phase 1 study utilizing a modified "3+3" dose escalation followed by an expansion phase in patients with KRAS G12 mutation, class-3 BRAF mutation, NF1 LOF mutation or RTK mutation, amplification or rearrangement advanced solid tumors. The primary objective is to determine safety and tolerability of BPI-442096, the MTD and RP2D. The secondary objectives are to assess the pharmacokinetic (PK) and pharmacodynamic (PD) profile, preliminary anti-tumor activity of BPI-442096.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed informed consent;
- •Age ≥18 and ≤75 years, male and female patients;
- •Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1;
- •Dose escalation phase: histologically or cytologically confirmed locally advanced or metastatic solid tumor patients (excluding HCC patients), who had disease progression after standard therapy, intolerable to standard therapy, refuse to standard therapy or for whom no standard therapy exists;
- •Dose expansion phase: histologically or cytologically confirmed locally advanced non-small cell lung cancer, pancreatic cancer, colorectal cancer or other diagnosed solid tumor patients (excluding HCC patients), who had disease progression after standard therapy, intolerable to standard therapy, refuse to standard therapy or for whom no standard therapy exists;
- •Evaluable lesion required for dose escalation phase and at least 1 measurable lesion as per RECIST v1.1 required for dose expansion phase;
- •Dose expansion only: Patients must have confirmation of tumour mutation status (including KRAS G12, Class-3 BRAF, NF1 LOF mutations, RTK mutations, amplifications or rearrangements).
- •Adequate organ function;
排除标准
- •Patients who have previously received a SHP2 inhibitor;
- •Inadequate wash-out of prior therapies described per protocol, which may include anti-tumor therapies, tumor adjuvant drugs, organ or stem cell transplantation, moderate or strong CYP3A inhibitor or inducer;
- •Patients with severe or unstable systemic disease, unstable/symptomatic CNS metastasis, other malignant tumors, autoimmune disease, ILD, cardiac disease, bleeding or embolic disease, infectious disease, conditions affecting drug swallow and absorption, medical history leading to chronic diarrhea, etc;
- •Pregnancy or lactation;
- •Other conditions considered not appropriate to participate in this trial by the investigators.
研究组 & 干预措施
Dose Escalation
Oral tablets taken in escalating levels to determine MTD/RP2D. Each treatment cycle will be 21 days in duration with BPI-442096 administered, once daily (QD).
干预措施: BPI-442096 (Drug)
Dose Expansion
Oral tablets administered at MTD/RP2D defined dose. Each treatment cycle will be 21 days in duration with BPI-442096 administered, once daily (QD)
干预措施: BPI-442096 (Drug)
结局指标
主要结局
Determine the recommended Phase II dose (RP2D)
时间窗: Through the Phase I, approximately 24 months
Number of subjects with dose limiting toxicity
The adverse events (AEs)
时间窗: Through the Phase I, approximately 24 months
Safety and tolerability will be assessed by monitoring frequency, duration and severity of adverse events (AEs).
次要结局
- AUC0-t(Through the Phase I, approximately 24 months)
- Cmax(Through the Phase I, approximately 24 months)
- Duration of response (DOR）(Through the Phase I, approximately 24 months)
- Progression free survival (PFS)(Through the Phase I, approximately 24 months)
- Tmax(Through the Phase I, approximately 24 months)
- t1/2(Through the Phase I, approximately 24 months)
- the objective response rate (ORR）(Through the Phase I, approximately 24 months)
- Disease control rate (DCR）(Through the Phase I, approximately 24 months)