A Phase 1 First-in-Human Open-Label Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy of ERAS-0015 Monotherapy and in Combination in Patients Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- Erasca, Inc.
- 入组人数
- 600
- 试验地点
- 9
- 主要终点
- Time to achieve Cmax (Tmax)
研究概览
简要总结
The main purpose of the study is to assess whether the study drug, ERAS-0015, is safe and tolerable when administered to patients with advanced or metastatic solid tumors with certain RAS mutations. ERAS-0015 will be given alone or in combination with other treatments.
详细描述
This is a first-in-human, Phase 1/1b, open-label, multicenter clinical study of ERAS-0015 as a monotherapy and in combination with other cancer therapies. The study will commence with dose optimization of ERAS-0015 monotherapy, followed by dose optimization of ERAS-0015 in combination with other cancer therapies.
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 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 18 years
- •Willing and able to give written informed consent
- •Pathological documentation of tumor type and mutation prior to the first dose of study drug(s), for applicable cohorts.
- •There is no available standard systemic therapy available for the patient's tumor histology and/or molecular biomarker profile; or standard therapy is intolerable, not effective, or not accessible; or patient has refused standard therapy. Does not apply to newly diagnosed Pancreatic Ductal Carcinoma (PDAC) cohort.
- •Able to swallow oral medication
- •Have Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1
- •Adequate cardiovascular, hematological, liver, and renal function
- •Willing to comply with all protocol-required visits, assessments, and procedures
排除标准
- •Previous treatment with a RAS inhibitor
- •Is currently receiving another study therapy or has participated in a study of an investigational agent and received study therapy within 4 weeks of the first dose of ERAS-0015
- •Received prior palliative radiation within 14 days of Cycle 1, Day 1
- •Have primary central nervous system (CNS) tumors
- •Prior surgery (e.g., gastric bypass surgery, gastrectomy) or gastrointestinal dysfunction (e.g., Crohn's disease, ulcerative colitis, short gut syndrome) that may affect drug absorption
- •Have any underlying medical condition, psychiatric condition, or social situation that, in the opinion of the Investigator, would compromise study administration as per protocol or compromise the assessment of AEs
- •Are pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the trial
研究组 & 干预措施
ERAS-0015 Monotherapy Dose Optimization.
Escalating doses of ERAS-0015 administered orally.
干预措施: ERAS-0015 (Drug)
ERAS-0015 Combination Dose Optimization
ERAS-0015 administered orally with another investigational agent.
干预措施: ERAS-0015 in combination (Drug)
结局指标
主要结局
Time to achieve Cmax (Tmax)
时间窗: Study Day 1 up to 65
Time to achieve maximum plasma concentration of ERAS-0015
Area under the curve
时间窗: Study Day 1 up to 65
Area under the plasma concentration-time curve of ERAS-0015
Dose Limiting Toxicities (DLT)
时间窗: Study Day 1 up to Day 21
Based on toxicities observed
Plasma concentration (Cmax)
时间窗: Study Day 1 up to 65
Maximum plasma concentration of ERAS-0015
Maximum tolerated dose (MTD)
时间窗: Study Day 1 up to Day 21
Based on toxicities observed
Half-life
时间窗: Study Day 1 up to 65
Half-life of ERAS-0015
Recommended dose for expansion (RDE)
时间窗: Study Day 1 up to Day 21
Based on toxicities observed
Adverse Events
时间窗: Study Day 1 up to Day 21
Incidence and severity of treatment-emergent AEs and serious AEs
次要结局
- Objective Response Rate (ORR)(Assessed up to 24 months from time of first dose)
- Duration of Response (DOR)(Assessed up to 24 months from time of first dose)
- Time to Response (TTR)(Assessed up to 24 months from time of first dose)