A Phase 1, Open-Label, Multicenter, Dose Escalation and Confirmation Study of PRT2527 in Participants With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 30
- 试验地点
- 8
- 主要终点
- Dose limiting toxicities (DLT) of PRT2527
研究概览
简要总结
This is a Phase 1 dose-escalation and confirmation study of PRT2527, a Cyclin-dependent Kinase 9 (CDK9) inhibitor, in participants with advanced solid tumors. The purpose of this study is to define the dosing schedule, and maximally tolerated dose to be used in subsequent development of PRT2527.
详细描述
This is a multicenter, open-label, dose-escalation and confirmation Phase 1 study of PRT2527, a CDK9 inhibitor, evaluating participants with selected advanced/metastatic sarcomas displaying a documented gene fusion, castrate resistant prostate cancer, hormone receptor positive HER2-negative breast cancer, advanced/metastatic non-small cell lung cancer, and solid tumors displaying MYC amplification. The study plan expects to evaluate approximately six dose levels of approximately 1-6 participants per dose level; however additional and/or intermediate dose levels may be explored. Taking into account pharmacokinetic and pharmacodynamic data from the preceding dose levels, the dose may be escalated until a dose limiting toxicity is identified. The total sample size will be approximately 30 patients for MTD and RP2D determination.
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
- •Tumor types under study
- •Selected sarcomas with a documented gene fusion
- •Castrate resistant prostate cancer (CRPC)
- •Hormone receptor positive (HR+), HER2 negative (HER2-) breast cancer
- •Non-small cell lung cancer (NSCLC)
- •MYC amplified solid tumors
- •Must have measurable disease per RECIST 1.1; participants with CRPC or sarcoma may have nonmeasurable but evaluable disease
- •Eastern Cooperative Oncology Group (ECOG) Performance Score of 0 or 1
- •Adequate organ function
- •Must provide tumor tissue sample to the central laboratory for biomarker analysis
- •Participants must have recovered from the effects of prior cancer-related therapy, radiotherapy, or surgery to ≤ Grade 1
排除标准
- •Primary malignancies of the CNS, or uncontrolled CNS metastases, including impending spinal cord compression
- •have a corrected QT interval >480 msec from prior or baseline
- •have impaired cardiac function or clinically significant cardiac disease
- •Treatment with strong inhibitors or inducers of CYP3A4
- •Prior exposure to a CDK9 inhibitor
- •History of another malignancy except for:
- •Curatively treated malignancy with no known active disease
- •Curatively treated non-melanoma skin cancer without evidence of disease
- •Curatively treated carcinoma in situ without evidence of disease
- •have undergone major surgery within 2 weeks prior to Week 1 Day 1
- •have had chemotherapy, biologic therapy, targeted therapy, immunotherapy, extended-field radiotherapy, or investigational agents within 5 half-lives or 28 days (whichever is shorter) prior to administration of the first dose of study drug on Week 1 Day 1.
研究组 & 干预措施
PRT2527
PRT2527 will be administered by intravenous infusion
干预措施: PRT2527 (Drug)
结局指标
主要结局
Dose limiting toxicities (DLT) of PRT2527
时间窗: Baseline through Day 21
Dose limiting toxicities will be evaluated over the 21-day observation period
Maximally tolerated dose (MTD) of PRT2527
时间窗: Baseline through approximately 1 year
The MTD will be established for further investigation in participants with advanced solid tumors
Recommended phase 2 dose (RP2D) and schedule of PRT2527
时间窗: Baseline through approximately 1 year
The RP2D will be established for further investigation in participants with advanced solid tumors
次要结局
- Safety and tolerability of PRT2527: AEs, SAEs, CTCAE assessments(Baseline through approximately 2 years)
- Pharmacokinetic profile of PRT2527: maximum observed plasma concentration(Baseline through approximately 1 year)
- Anti-tumor activity of PRT2527: measurement of objective responses(Baseline through approximately 2 years)
- Duration of response to PRT2527: Objective responses(Baseline through approximately 2 years)