A Phase 1, First-in-Human Study of the SMARCA2 Degrader, PLX-61639, in Patients With SMARCA4-Mutated Locally Advanced or Metastatic Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 155
- 试验地点
- 11
- 主要终点
- Treatment Emergent Adverse Events
研究概览
简要总结
A multicenter, single-arm, first-in-human study to investigate the safety, pharmacokinetics, and preliminary antitumor activity of PLX-61639 in participants with locally advanced or metastatic, relapsed/refractory, SMARCA4-deficient solid tumors who are intolerant of or have failed available, approved therapies.
The study will be conducted in 3 parts: dose escalation (Part 1), dose optimization (Part 2), and cohort expansion (Part 3). Each part of the study will consist of a Screening Phase lasting up to 28 days during which participants will be assessed for eligibility, a Treatment Phase beginning on Cycle 1 Day 1 and consisting of consecutive 28-day cycles, an End of Treatment Visit, and a Post-Treatment Follow-Up Phase.
Participants will receive their assigned dose of PLX-61639 administered orally, once daily until progression/relapse, intolerance, death, or withdrawal from study treatment by the Investigator or participant.
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
- •Participants with locally advanced or metastatic, relapsed/refractory, solid tumors harboring a SMARCA4 loss-of-function mutation that have progressed on, are intolerant of, or not otherwise candidates for available approved therapies
- •Adequate liver bone marrow, coagulation, renal, and cardiopulmonary function
- •Measurable disease per RECIST 1.1
- •ECOG PS of 0 or 1
排除标准
- •Germline SMARCA4 mutations
- •Known SMARCA2 mutation or loss of expression
- •Symptomatic CNS disease
- •Prior treatment with another SMARCA2-directed therapy
- •History of other malignancies
- •Clinically significant heart disease
- •Uncontrolled hypertension
- •Prolongation of QT interval
研究组 & 干预措施
PLX-61639
干预措施: PLX-61639 (Drug)
结局指标
主要结局
Treatment Emergent Adverse Events
时间窗: From enrollment to 28 days after the last dose of PLX-61639
Dose-Limiting Toxicities
时间窗: From enrollment to 28 days after first dose of PLX-61639
次要结局
- Study treatment discontinuations for reasons other than disease progression(From Day 1 to the end of PLX-61639 treatment, an average of 1 year)
- Dose reductions due to Adverse Events(From Day 1 to the end of PLX-61639 treatment, an average of 1 year)
- Pharmacokinetics of PLX-61639: Cmax(From Day 1 to Day 15 of Cycle 1 (Part 1 only) (each cycle is 28 days))
- Pharmacokinetics of PLX-61639: Tmax(From Day 1 to Day 15 of Cycle 1 (Part 1 only) (each cycle is 28 days))
- Pharmacokinetics of PLX-61639: AUC0-last(From Day 1 to Day 16 of Cycle 1 (Part 1 only) (each cycle is 28 days))
- Radiographic response to PLX-61639(From Day 1 to the end of PLX-61639 treatment, an average of 1 year)
- Time to response (TTR) to PLX-61639(From Day 1 to achievement of partial or complete response, up to 24 weeks)
- Duration of response (DoR) to PLX-61639(From first documented partial or complete response to disease progression or death, an average of 1 year)
- Progression Free Survival (PFS) of PLX-61639(From Day 1 to disease progression or death, an average of 1 year)