A Multicenter, Open Phase I/IIa Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Antitumor Activity of JAB-23E73 in Patients With Advanced Solid Tumors Harboring KRAS Gene Alteration
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 334
- 试验地点
- 4
- 主要终点
- Phase 1: Number of participants with dose limiting toxicities (DLT)
研究概览
简要总结
This is a multicenter, open-label, phase I/IIa to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and preliminary antitumor activity of pan-KRAS inhibitor JAB-23E73 in patients with advanced solid tumors harboring KRAS mutations or amplification. The study consists of 2 phases: Phase 1 Dose Escalation and Phase IIa Dose Expansion.
详细描述
Study JAB-23E73-1001 is a global multicenter, open-label Phase 1/2a study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary anticancer activity of JAB-23E73 as a single agent in adult patients with advanced solid tumors with KRAS alteration. This study consists of a Phase 1a dose-escalation, followed by Phase 1b dose-expansion (dose optimization) and Phase 2a indication expansion. After completing dose-escalation, the MTD or preliminary RP2D of JAB-23E73 will be determined. Then, two of the alternative dosages of JAB-23E73 will be selected to further evaluate the efficacy, safety and PK in patients with KRAS-alternated NSCLC or other tumors, and patients may be further selected by certain/several types of KRAS-alternations based on dose escalation data. The RP2D will be determined according to the safety, efficacy and PK data from phase 1b.
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
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histological or cytologically proven diagnosis of a locally advanced, unresectable, and/or metastatic solid tumor cancer with evidence of KRAS gene alteration (including gene mutation and wild type amplification).
- •Able to provide an archived tumor tissue sample or fresh biopsy sample.
- •Life expectancy ≥3 months at the start of treatment.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •≥1 measurable lesion per RECIST v1.
- •Adequate organ function.
排除标准
- •Unable to swallow oral medications or with gastrointestinal dysfunction or gastrointestinal disease that significantly alters the absorption of medication.
- •Previous treatment with rat sarcoma (RAS) targeting agents.
- •Symptomatic, untreated, or actively progressing known central nervous system (CNS) metastases.
- •Impaired cardiovascular function or clinically significant cardiac disease.
- •Mean QT interval corrected using Fridericia's formula (QTcF) >470 msec.
- •Females who are pregnant or breastfeeding.
研究组 & 干预措施
Phase 2a Dose Expansion
Monotherapy, dose expansion
干预措施: JAB-23E73 (Drug)
Phase 1 Dose Exploration
Monotherapy, dose escalation
干预措施: JAB-23E73 (Drug)
结局指标
主要结局
Phase 1: Number of participants with dose limiting toxicities (DLT)
时间窗: Up to 21 days
Incidence of dose limiting toxicities (DLTs) in the dose escalation phase. DLTs will be defined as the occurrence of any of the toxicities as described in the protocol.
Phase 2a: Objective response rate (ORR)
时间窗: Up to approximately 2 years
ORR is defined as the proportion of patients with a best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR) per RECIST v1.1.
次要结局
- Phase 1/2a: PK: Time to Maximum Concentration (Tmax) of JAB-23E73(Up to approximately 2 years)
- Phase 1/2a: PK: Area Under the Concentration Versus Time Curve (AUC) of JAB-23E73(Up to approximately 2 years)
- Phase 1: ORR(Up to approximately 2 years)
- Phase 1/2a: Safety and Tolerability(Up to approximately 2 years)
- Phase 1/2a: Pharmacokinetic (PK): Maximum concentration (Cmax) of JAB-23E73(Up to approximately 2 years)
- Phase 1/2a: Time to Response (TTR)(Up to approximately 2 years)
- Phase 1/2a: Progression Free Survival (PFS)(Up to approximately 2 years)
- Phase 1/2a: Disease Control Rate (DCR)(Up to approximately 2 years)
- Phase 1/2a: Duration of Response (DoR)(Up to approximately 2 years)
- Phase 2a: Overall Survival (OS)(Up to approximately 2 years)