An Open-Label, Multi-Center Phase 1/1b Dose Escalation and Expansion Study of ERAS-601 SHP2 Inhibitor as a Monotherapy and in Combination With Other Anti-Cancer Therapies in Patients With Advanced or Metastatic Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- Erasca, Inc.
- 入组人数
- 200
- 试验地点
- 14
- 主要终点
- Half-life
研究概览
简要总结
- To evaluate the safety and tolerability of escalating doses of ERAS-601 when administered as a monotherapy and in combination with other cancer therapies in study participants with advanced or metastatic solid tumors.
- To determine the Maximum Tolerated Dose (MTD) and/or recommended dose (RD) of ERAS-601 when administered as a monotherapy and in combination with other cancer therapies.
- To characterize the pharmacokinetic (PK) profile of ERAS-601 when administered as a monotherapy and in combination with other cancer therapies.
- To evaluate the antitumor activity of ERAS-601 when administered as a monotherapy and in combination with other cancer therapies.
详细描述
This is a first-in-human, Phase 1/1b, open-label, multicenter clinical study of ERAS-601 as a monotherapy and in combination with other cancer therapies. The study will commence with dose escalation of ERAS-601 monotherapy, followed by dose escalation of ERAS-601 in combination with other cancer therapies. Once the monotherapy MTD and/or RD has been determined, then dose expansion of ERAS-601 monotherapy may commence with enrollment of study participants with advanced or metastatic solid tumors harboring specific molecular alterations. Once the combination therapy MTD and/or RD has been determined, then dose expansion of that combination may commence with enrollment of study participants with advanced or metastatic solid tumors harboring specific molecular alterations.
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
- •Have histologically or cytologically confirmed advanced or metastatic solid tumor
- •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
- •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 SHP2 inhibitor
- •Documented PTPN11 mutations
- •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-601
- •Received prior palliative radiation within 7 days of Cycle 1, Day 1
- •Have primary central nervous system (CNS) disease or known active CNS metastases and/or carcinomatous meningitis
- •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
- •Active, clinically significant interstitial lung disease or pneumonitis
- •History of thromboembolic or cerebrovascular events ≤ 12 weeks prior to the first dose of study treatment
- •History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO
- •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
Dose Escalation (Part A): ERAS-601 monotherapy
ERAS-601 monotherapy will be administered in sequential ascending doses to study participants with advanced or metastatic solid tumors until unacceptable toxicity, disease progression, or withdrawal of consent.
干预措施: ERAS-601 (Drug)
Dose Escalation (Part B): ERAS-601 monotherapy
ERAS-601 monotherapy will be administered in sequential ascending doses to study participants with advanced or metastatic solid tumors until unacceptable toxicity, disease progression, or withdrawal of consent.
干预措施: ERAS-601 (Drug)
Dose Escalation (Part C): ERAS-601 monotherapy
ERAS-601 will be administered in sequential ascending doses to study participants with advanced or metastatic solid tumors until unacceptable toxicity, disease progression or withdrawal of consent.
干预措施: ERAS-601 (Drug)
Dose Escalation and Dose Expansion (Part D): ERAS-601 in combination with cetuximab
ERAS-601 will be administered in sequential ascending doses with cetuximab to study participants with advanced metastatic solid tumors until unacceptable toxicity, disease progression or withdrawal of consent. Once the combination therapy recommended dose has been determined, this will be administered to study participants with HPV negative advanced or metastatic head and neck squamous cell carcinoma (HNSCC) or colorectal cancer (CRC).
干预措施: ERAS-601 (Drug)
Dose Escalation and Dose Expansion (Part D): ERAS-601 in combination with cetuximab
ERAS-601 will be administered in sequential ascending doses with cetuximab to study participants with advanced metastatic solid tumors until unacceptable toxicity, disease progression or withdrawal of consent. Once the combination therapy recommended dose has been determined, this will be administered to study participants with HPV negative advanced or metastatic head and neck squamous cell carcinoma (HNSCC) or colorectal cancer (CRC).
干预措施: Cetuximab (Drug)
Dose Escalation and Dose Expansion (Part E): ERAS-601 in combination with pembrolizumab
ERAS-601 will be administered in sequential ascending doses with pembrolizumab to study participants with advanced metastatic solid tumors until unacceptable toxicity, disease progression or withdrawal of consent. Once the combination therapy recommended dose has been determined, this will be administered to study participants with HPV negative advanced or metastatic head and neck squamous cell carcinoma (HNSCC) or non small cell lung cancer (NSCLC).
干预措施: ERAS-601 (Drug)
Dose Escalation and Dose Expansion (Part E): ERAS-601 in combination with pembrolizumab
ERAS-601 will be administered in sequential ascending doses with pembrolizumab to study participants with advanced metastatic solid tumors until unacceptable toxicity, disease progression or withdrawal of consent. Once the combination therapy recommended dose has been determined, this will be administered to study participants with HPV negative advanced or metastatic head and neck squamous cell carcinoma (HNSCC) or non small cell lung cancer (NSCLC).
干预措施: Pembrolizumab (Drug)
结局指标
主要结局
Half-life
时间窗: Study Day 1 up to Day 29
Half-life of ERAS-601 and cetuximab or pembrolizumab (if applicable)
Area under the curve
时间窗: Study Day 1 up to Day 29
Area under the plasma concentration-time curve of ERAS-601 and cetuximab or pembrolizumab (if applicable)
Dose Limiting Toxicities (DLT)
时间窗: Study Day 1 up to Day 29
Based on toxicities observed
Plasma concentration (Cmax)
时间窗: Study Day 1 up to Day 29
Maximum plasma concentration of ERAS-601 and cetuximab or pembrolizumab (if applicable)
Time to achieve Cmax (Tmax)
时间窗: Study Day 1 up to Day 29
Time to achieve maximum plasma concentration of ERAS-601 and cetuximab or pembrolizumab (if applicable)
Recommended dose (RD)
时间窗: Study Day 1 up to Day 29
Based on toxicities observed
Maximum tolerated dose (MTD)
时间窗: Study Day 1 up to Day 29
Based on toxicities observed
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
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)