A Phase 1/1b Open-Label, Multicenter, First-in-Human Study Evaluating Safety, Tolerability, Pharmacokinetics, and Antitumor Activity of RGT-490 as a Single Agent in Adult Subjects With Locally Advanced or Metastatic PIK3CA-Mutated Solid Tumors Including HR+/HER2- Breast Cancers
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 63
- 试验地点
- 5
- 主要终点
- Incidence of dose limiting toxicities (DLTs)
研究概览
简要总结
This is a phase 1/1b, open-label, multicenter study consisting of sequential parts designed to evaluate the safety, tolerability, and effects pharmacokinetic (PK) profile, and antitumor activity of RGT-490, an investigational oral therapy, in adults with locally advanced or metastatic solid tumors including breast cancer.
Participants enrolled in the study have advanced disease that is not amendable to curative treatment and whose tumors harbor alterations in the PI3KCA gene.
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
- •Adults with metastatic or locally advanced, unresectable solid tumors that have progressed on or after at least one available therapy.
- •Presence of one or more documented activating PIK3CA mutation in tumor tissue and/or blood.
- •At least 1 measurable lesion or evaluable disease per RECIST v1.
- •An ECOG performance status of 0 or
- •Adequate organ function
排除标准
- •Diabetes mellitus requiring anti-hyperglycemic medication.
- •Prior treatment with PI3Kα inhibitors
- •Symptomatic, untreated, or uncontrolled central nervous system metastases.
- •Receipt of any local or systemic anticancer therapy or investigational anticancer agent within a protocol-defined washout period prior to study treatment.
- •Unresolved clinically significant toxicities from prior anticancer therapy
- •History of a another malignancy within 2 years prior to screening (exception adequately treated cancers).
研究组 & 干预措施
Phase 1 Dose Escalation (Advanced Solid Tumors with PIK3CA mutation)
RGT-490 given alone as monotherapy
干预措施: RGT-490 (Drug)
Phase 1b Dose Expansion (HR+/HER2- locally advanced or metastatic breast cancer)
RGT-490 given alone as monotherapy
干预措施: RGT-490 (Drug)
结局指标
主要结局
Incidence of dose limiting toxicities (DLTs)
时间窗: 4 weeks (1 cycle)
Number of subjects who experience at least 1 Dose Limiting Toxicity (DLT)
Incidence and grade of Adverse Events (AEs) and Serious Adverse Events (SAEs)
时间窗: Every cycle (4-week cycles) until study discontinuation, approximately 12 months
Incidence and grade of Adverse Events (AEs) and Serious Adverse Events (SAEs) and AEs leading to dose modifications and dose limiting toxicities (DLTs) to determine the maximum tolerated dose (MTD)
次要结局
- Characterize the Cmax (PK) of RGT-490 monotherapy in Dose Escalation(First 3 treatment cycles (each cycle is 28 days))
- Characterize the Tmax (PK) of RGT-490 monotherapy in Dose Escalation(First 3 treatment cycles (each cycle is 28 days))
- Characterize the AUC (PK) of RGT-490 monotherapy in Dose Escalation(First 3 treatment cycles (each cycle is 28 days))
- Measure PD effects of RGT-490 monotherapy in Dose Escalation and Phase 1b(First 7 cycles (each cycle is 28 days) and at study discontinuation)
- Changes in fasting blood glucose(Approximately every week in Cycle 1 and Cycle 2 (4-week cycle), every 2 weeks in Cycles 3-6 (4-week cycle), and every cycle through end of treatment (4-week cycles), approximately 24 months)
- Changes in longitudinal glucose metabolism (All Phases)(Approximately every cycle (4-week cycles) until study discontinuation, approximately 24 months)
- Assess preliminary efficacy of RGT-490 monotherapy in dose escalation and Phase 1b(Approximately every 8 weeks until progressive disease, approximately 12 months)
- Evaluate additional measures of efficacy of RGT-490(Approximately every 8 weeks until progressive disease, approximately 36 months)