A Phase 1 Study to Evaluate the CNS-Penetrant EGFR/ERBB1 Inhibitor ERAS-801 in Patients With Recurrent Glioblastoma (THUNDERBBOLT-1)
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 52
- 试验地点
- 8
- 主要终点
- Dose Limiting Toxicities (DLT)
研究概览
简要总结
- To evaluate the safety and tolerability of escalating doses of ERAS-801 in study participants with recurrent glioblastoma multiforme (GBM).
- To determine the Maximum Tolerated Dose (MTD) and/or Recommended Dose (RD) of ERAS-801.
- To evaluate the antitumor activity of ERAS-801.
- To evaluate the PK profile of ERAS-801.
详细描述
This is a Phase 1, open-label, multicenter clinical study evaluating ERAS-801 as a monotherapy. The study will initially commence with dose escalation of ERAS-801 in study participants with recurrent GBM. Once the MTD and/or RD has been determined from dose escalation, then dose expansion of ERAS-801 may commence in study participants with recurrent GBM harboring alterations in epidermal growth factor receptor (EGFR).
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
- •Diagnosis of Glioblastoma, IDH WT as defined by the WHO 2021 criteria
- •Adequate organ function
- •Willing to comply with all protocol-required visits, assessments, and procedures
- •Able to swallow oral medication
排除标准
- •Prior treatment with an EGFR inhibitor for Glioblastoma
- •Currently enrolled in another therapeutic study
- •History of clinically significant cardiovascular disease
- •Gastrointestinal conditions that may affect administration/absorption of oral medications
- •Have an active infection (bacterial, fungal, or viral) requiring systemic therapy
- •Pregnant or breastfeeding women
- •Any serious underlying medical or psychiatric condition or evidence of any other significant clinical disorder or laboratory finding that renders the patient inappropriate to participate in the study
- •Known allergies, hypersensitivity, or intolerance to ERAS-801 or its excipients
研究组 & 干预措施
Dose Escalation (Part 1)
ERAS-801 will be orally administered to study participants with recurrent GBM in sequential ascending doses until unacceptable toxicity, disease progression, or withdrawal of consent.
干预措施: ERAS-801 (Drug)
Dose Expansion (Part 2)
ERAS-801 will be orally administered at the recommended dose (as determined from Part 1) to study participants with recurrent GBM harboring alterations in EGFR.
干预措施: ERAS-801 (Drug)
结局指标
主要结局
Dose Limiting Toxicities (DLT)
时间窗: Study Day 1 up to Day 29
Based on adverse events observed during dose escalation
Maximum Tolerated Dose (MTD)
时间窗: Study Day 1 up to Day 29
Based on adverse events observed during dose escalation
Adverse Events
时间窗: Assessed up to 24 months from time of first dose
Incidence and severity of treatment-emergent AEs and serious AEs
Recommended Dose (RD)
时间窗: Study Day 1 up to Day 29
Based on adverse events observed during dose escalation
次要结局
- Half-life(Study Day 1 up to Day 29)
- Area under the curve(Study Day 1 up to Day 29)
- Plasma concentration (Cmax)(Study Day 1 up to Day 29)
- 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)
- Time to achieve Cmax (Tmax)(Study Day 1 up to Day 29)
- Objective Response Rate (ORR)(Assessed up to 24 months from time of first dose)