A Phase 1 Open-Label, Multi-Center, Safety and Efficacy Study of PRT7732, an Oral SMARCA2 Degrader, in Patients With Advanced or Metastatic Solid Tumors With a SMARCA4
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 42
- 试验地点
- 28
- 主要终点
- Safety and tolerability of PRT7732 as measured by incidence of laboratory deviations
研究概览
简要总结
This is a Phase 1 study to determine the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of PRT7732 in patients with select advanced or metastatic solid tumors with a SMARCA4 mutation.
详细描述
This is an open-label, multi-center, first-in-human, Phase 1 study to determine the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of PRT7732 an oral SMARCA degrader in patients with select advanced or metastatic solid tumors with a SMARCA4 mutation. Approximately 104 participants will be enrolled.
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
- •Willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations (including contraception requirements), and other study procedures
- •Histologically confirmed advanced, recurrent, or metastatic solid tumor malignancy with any mutation of SMARCA4 by local testing that has either progressed on or is ineligible for standard of care therapy
- •Must have measurable or non-measurable (but evaluable) disease per RECIST v1.1
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- •Willing to provide either archival or fresh tumor tissue sample
- •Adequate organ function (hematology, renal, and hepatic)
排除标准
- •Participants with solid tumors with known concomitant SMARCA2 mutation or loss of protein expression
- •Clinically significant or uncontrolled cardiac disease, uncontrolled electrolyte disorders, uncontrolled or symptomatic central nervous system (CNS) metastases or leptomeningeal disease
- •History of other malignancy within 3 years except for adequately treated basal cell or squamous cell skin cancer, superficial bladder cancer, prostate intraepithelial neoplasm, prostate adenocarcinoma with Gleason score of 3+3 or less, carcinoma in situ of the cervix, or other non-invasive or indolent malignancies, or malignancies previously treated with curative intent and not on active therapy or expected to require treatment or recurrence during the study
- •Receipt of any targeted therapy directed against BRM/BRG1 (SMARCA2/SMARCA4).
研究组 & 干预措施
PRT7732
PRT7732 is administered as an oral capsule once daily. Dose escalation/de-escalation decisions will be guided by the BLRM method until the RDE is determined.
干预措施: PRT7732 (Drug)
结局指标
主要结局
Safety and tolerability of PRT7732 as measured by incidence of laboratory deviations
时间窗: Baseline through study completion, an average of 2 years
Safety and tolerability will be evaluated by laboratory measurements
Recommended dose for expansion (RDE) of PRT7732
时间窗: Baseline through study completion, an average of 2 years
The RDE will be determined by the sponsor based on the Safety Review Committee's recommendation considering the totality of the available clinical safety, clinical efficacy, pharmacokinetics (PK), and pharmacodynamic data
Safety and tolerability of PRT7732 as measured by incidence of DLTs
时间窗: Baseline through completion of study, an average of 2 years
Safety and tolerability will be evaluated by incidence of DLTs
Dose Limiting toxicity (DLT) of PRT7732
时间窗: Baseline through Day 21
Incidence of dose limiting toxicities for patients in the dose escalation phase
Safety and tolerability as measured by rates of dose modification due to AEs according to NCI CTCAE
时间窗: Baseline through study completion, an average of 2 years
Safety and tolerability will be evaluated by dose interruption, modification, and discontinuation due to adverse events (AEs) according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE)
Maximum tolerated dose (MTD) of PRT7732
时间窗: Baseline through study completion, an average of 2 years
Maximum tolerated dose will be determined by the sponsor based on the Safety Review Committee's recommendation considering the totality of the available clinical safety, clinical efficacy, pharmacokinetics (PK), and pharmacodynamic data
次要结局
- Efficacy of PRT7732(Baseline through study completion, an average of 2 years)
- Pharmacokinetic profile of PRT7732 as a single agent: Time of maximum concentration (Tmax) and half-life (T1/2)(Baseline through study completion, an average of 2 years)
- Pharmacodynamic effects of PRT7732 as a single agent(Baseline through study completion, an average of 2 years)
- Pharmacokinetic profile of PRT7732 as a single agent: Area under the curve(Baseline through study completion, an average of 2 years)
- Pharmacokinetic profile of PRT7732 as a single agent: Maximum observed plasma concentration(Baseline through study completion, an average of 2 years)