An Open-label Study to Assess the Safety and Efficacy of Naporafenib (ERAS-254) Administered With Trametinib in Previously Treated Patients With Locally Advanced Unresectable or Metastatic Solid Tumor Malignancies With RAS Q61X Mutations
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
- 86
- 试验地点
- 29
- 主要终点
- To evaluate the efficacy of naporafenib administered with trametinib in patients with rat sarcoma viral oncogene (RAS) Q61X solid tumors
研究概览
简要总结
To evaluate the efficacy of naporafenib administered with trametinib in patients with rat sarcoma viral oncogene (RAS) Q61X solid tumors
- To evaluate the safety and tolerability of naporafenib administered with trametinib in patients with RAS Q61X solid tumors
- To characterize the pharmacokinetic (PK) profile of naporafenib and trametinib when administered to patients with RAS Q61X solid tumors
详细描述
SEACRAFT-1 is an open-label study to assess the safety and efficacy of naporafenib administered with trametinib in previously treated patients with locally advanced unresectable or metastatic RAS Q61X solid tumor malignancies. The study will enroll a total of approximately 100 adult patients; a sub-study will enroll approximately 15 adolescent patients ≥12 and <18 years for a total sample size of approximately 115. Patients with a locally advanced unresectable or metastatic solid tumor malignancy that is not responsive to standard therapies or for which there is no standard therapy are eligible. Patients with primary central nervous system (CNS) tumors are not eligible. Documentation of a RAS Q61X mutation in tumor tissue prior to the first dose of study treatment is required.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 12 Years 至 99 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Willing and able to provide written informed consent
- •Age ≥ 12 years
- •A locally advanced or metastatic tumor who has progressed on or for which no standard therapy exists. Patients who are intolerant to standard therapy or who are not a candidate for standard therapy (in the opinion of the Investigator) or who decline standard therapy are also eligible.
- •Documentation of a RAS Q61X mutation (tumor tissue or blood) prior to first dose of study treatment as determined locally with an analytically validated assay in a certified testing laboratory.
- •Archival tumor tissue collected within 5 years prior to enrollment must be confirmed to be available at the time of Screening, which may be submitted before or after enrollment for exploratory biomarker analysis.
- •ECOG performance status 0, 1 or 2
- •Presence of at least 1 measurable lesion according to RECIST v1.1
- •Able to swallow oral medication.
排除标准
- •Prior therapy with an ERK-, MEK-, RAF-, or RAS-inhibitor
- •Impairment of GI function or gastrointestinal (GI) disease that may significantly alter the absorption of study treatment (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection)
- •History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO (e.g., uncontrolled glaucoma or ocular hypertension, history of hyperviscosity or hypercoagulability syndrome)
- •Corrected QT interval using Fridericia's formula (QTcF) at Screening >450 ms based on triplicate average NOTE: criterion does not apply to patients with a right or left bundle branch block
- •All primary CNS tumors
- •Symptomatic CNS metastases that are neurologically unstable. Patients with controlled CNS metastases are eligible.
- •Patients receiving treatment with medications that are known to be strong inhibitors and/or inducers of cytochrome P450 (CYP)3A; substrates of CYP2C8, CYP2C9, and CYP3A with a narrow therapeutic index and sensitive substrates of CYP3A;
- •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
Naporafenib + Trametinib
Naporafenib (ERAS-254) 200 mg twice daily (BID) Trametinib 1 mg once daily (QD)
干预措施: Naporafenib (Drug)
Naporafenib + Trametinib
Naporafenib (ERAS-254) 200 mg twice daily (BID) Trametinib 1 mg once daily (QD)
干预措施: Trametinib (Drug)
结局指标
主要结局
To evaluate the efficacy of naporafenib administered with trametinib in patients with rat sarcoma viral oncogene (RAS) Q61X solid tumors
时间窗: Assessed up to 24 months from time of first dose
Based on assessment of Objective response rate (ORR) per RECIST version 1.1
次要结局
- Plasma concentration (Cmax)(Study Day 1 up to Day 29)
- Time to achieve Cmax (Tmax)(Study Day 1 up to Day 29)
- Area under the curve (AUC)(Study Day 1 up to Day 29)
- Adverse Events(Assessed up to 24 months from time of first dose)
- Duration of Response (DOR)(Assessed up to 24 months from time of first dose)
- Overall survival(Assessed up to 24 months from time of first dose)
- Time to Response (TTR)(Assessed up to 24 months from time of first dose)
- Progression Free Survival (PFS)(Assessed up to 24 months from time of first dose)
- Disease Control Rate (DCR)(Assessed up to 24 months from time of first dose)