A Phase 1/2, Open-label Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Prime Efficacy of PRJ1-3024 in Subjects with Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 267
- 试验地点
- 5
- 主要终点
- Incidence of dose-limiting toxicity (DLT) events during the DLT monitoring period
研究概览
简要总结
This is a multicenter, open-label study to assess the safety and preliminary efficacy and to determine the maximum tolerated dose (MTD) or maximum administration dose (MAD) and recommended Phase 2 doses (RP2D) of PRJ1-3024 in subjects with relapsed/refractory solid tumors. The study consists of two parts, one is a 3+3 dose escalation study and another is a pharmaceutical extension of RP2D.
详细描述
Using dose escalation, the study will evaluate the safety, tolerability, PK, and pharmacodynamics of PRJ1-3024 and will determine the maximum tolerated dose in subjects with advanced solid tumors.
Participants with advanced solid tumor will receive PRJ1-3024 daily as an oral therapy and test the impact of of PRJ1-3024 on tumors.
This study will find the safe and tolerable recommended dose in subjects with advanced solid tumors in a open-label, 3+3 dose escalation study and use the RP2D to assess the preliminary efficacy of PRJ1-3024 in a long-term extension study.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically or cytologically confirmed locally advanced (unresectable) or metastatic r/r solid tumors for which no standard therapy is available or for whom standard therapy is considered unsuitable or intolerable.
- •Male or non-pregnant, non-lactating female subjects age ≥18 years.
- •ECOG Performance Status 0~
- •Has at least 1 measurable lesion as defined by RECIST 1.1 criteria .
- •Life expectancy of >3 months, in the opinion of the Investigator.
- •Able to take oral medications and willing to record daily adherence to investigational product.
- •Adequate hematologic parameters unless clearly due to the disease under study.
- •Adequate renal and hepatic function
- •Able to understand and willing to sign a written informed consent form.
排除标准
- •History of another malignancy
- •Known symptomatic brain metastases requiring >10 mg/day of prednisolone.
- •Significant cardiovascular disease.
- •Known active HBV, HCV, AIDS-related illness.
- •Has received a live vaccine within 30 days.
- •History of active autoimmune disorders, or ongoing immunosuppressive therapy or ongoing .
- •Continuance of toxicities due to prior radiotherapy or chemotherapy agents that do not recover to < Grade
- •Receiving concurrent anti-cancer therapy, investigational product, strong inhibitors or inducers of cytochrome P450 3A (CYP3A) .
- •Prior treatment with hematopoietic progenitor kinase 1 (HPK1) inhibitors.
研究组 & 干预措施
Monotherapy Escalation
3+3 Dose escalation arm with PRJ1-3024 which will begin with 2 subjects treated at the lowest planned dose level. PRJ1-3024 is administered orally once daily. The starting dose is 80mg/day.
干预措施: PRJ1-3024 (Drug)
Monotherapy Exploration of the recommended dose
Upon completing Phase 1 and depending on data obtained, dose expansion may proceed in Phase 2 with several cohorts enrolled to confirm the tolerability of the RP2D of PRJ1-3024 (determined in Phase 1). PRJ1-3024 is administered orally once daily. The starting dose is determined by clinical effecacy data from Phase 1, and treatment may continue for up to 2 years as long as the subject experiences clinical benefit in the opinion of the Investigator and shows no signs or symptoms of unequivocal progression of disease.
干预措施: PRJ1-3024 (Drug)
结局指标
主要结局
Incidence of dose-limiting toxicity (DLT) events during the DLT monitoring period
时间窗: Day 1 to Day 21
Safety listings and pharmacokinetic listings will be used for evaluation
次要结局
- Incidence of adverse events (AEs)(24 months)
- Objective response rate (ORR)(24 months)
- Pharmacokinetic parameter#Maximum observed concentration (Cmax)(24 months)
- Pharmacokinetic parameter# Accumulation ratio(24 months)
- Pharmacokinetic parameter#AUC0-last#(24 months)
- Duration of response (DOR)(24 months)