A Phase 1b Master Protocol of Agents Targeting the Mitogen-Activated Protein Kinase Pathway in Patients With Advanced Non-Small-Cell Lung Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Erasca, Inc.
- 入组人数
- 24
- 试验地点
- 11
- 主要终点
- Recommended Dose (RD)
研究概览
简要总结
- To evaluate the safety and tolerability of escalating doses of ERAS-007 or ERAS-601 in combination with other cancer therapies in study participants with advanced non-small cell lung cancer (NSCLC).
- To determine the Maximum Tolerated Dose (MTD) and/or Recommended Dose (RD) of ERAS-007 or ERAS-601 administered in combination with other cancer therapies.
- To evaluate the antitumor activity of ERAS-007 or ERAS-601 in combination with other cancer therapies.
- To evaluate the PK profiles of ERAS-007 or ERAS-601 and other cancer therapies when administered in combination.
详细描述
This is a Phase 1b, open-label, multicenter master protocol evaluating safety, tolerability, and antitumor activity of ERAS-007 or ERAS-601 in combination with other cancer therapies in study participants with advanced NSCLC. The study will commence with the following dose escalation cohorts: ERAS-007 plus osimertinib in study participants with advanced NSCLC harboring epidermal growth factor receptor-sensitizing mutation(s) (EGFRm); ERAS-007 or ERAS-601 plus sotorasib in study participants with advanced NSCLC harboring Kirsten rat sarcoma G12C mutation (KRAS G12Cm). Dose expansion will follow and will evaluate ERAS-007 or ERAS-601 drug combinations administered at the RD identified from each respective dose escalation cohort in study participants with advanced EGFRm or KRAS G12Cm NSCLC.
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 NSCLC, with presence of EGFR mutation(s) sensitive to EGFR inhibitors, or KRAS G12C mutation.
- •Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.
- •Adequate bone marrow and organ function.
- •Have ECOG performance status of 0 or
- •Willing to comply with all protocol-required visits, assessments, and procedures.
- •Able to swallow oral medication.
排除标准
- •Concurrent treatment with any systemic anticancer therapy for NSCLC, including any approved or investigational agent.
- •For participants with EGFRm NSCLC: prior therapy with a RAS, RAF, MEK, or ERK inhibitor.
- •For participants with KRAS G12Cm NSCLC: prior therapy with a SHP2, ERK, or KRAS G12C inhibitor (depending on which cohort is being considered for enrollment).
- •Palliative radiotherapy within 7 days of enrollment.
- •History of unacceptable toxicity to treatment with osimertinib or sotorasib.
- •Major surgery within the 28 days of enrollment.
- •Unresolved toxicities from prior systemic therapy greater than NCI CTCAE grade 1 at time of enrollment, except for toxicities not considered a safety risk (eg, alopecia, vitiligo, and grade 2 neuropathy due to prior chemotherapy).
- •History of another malignancy ≤5 years prior to first dose, except for patients who are disease-free for >2 years after treatment with curative intent or who have carcinoma in situ.
- •Symptomatic and unstable brain metastases, or spinal cord compression, except for patients who have completed definitive therapy (surgery or radiotherapy), are not on steroids, and have a stable neurologic status for a least 2 weeks after completion of the definitive therapy and steroids.
- •History of or clinically active ILD, drug induced ILD, or radiation pneumonitis that required steroid treatment.
- •Impaired cardiovascular function or clinically significant cardiovascular disease.
- •History or current evidence of retinal pigment epithelial detachment (RPED), central serous retinopathy, retinal vein occlusion (RVO), or predisposing factors to RPED or RVO.
- •Any evidence of severe or uncontrolled systemic disease or evidence of any other significant clinical disorder or laboratory finding that renders the patient inappropriate to participate in the study.
- •Pregnant or breastfeeding women.
- •Contraindication to osimertinib or sotorasib use as per local label.
研究组 & 干预措施
Dose Escalation (Part 1): ERAS-007 plus osimertinib
ERAS-007 will be orally administered in combination with osimertinib to study participants with EGFRm NSCLC in sequential ascending doses until unacceptable toxicity, disease progression, or withdrawal of consent.
干预措施: ERAS-007 (Drug)
Dose Escalation (Part 1): ERAS-007 plus osimertinib
ERAS-007 will be orally administered in combination with osimertinib to study participants with EGFRm NSCLC in sequential ascending doses until unacceptable toxicity, disease progression, or withdrawal of consent.
干预措施: Osimertinib (Drug)
Dose Escalation (Part 2): ERAS-007 plus sotorasib
ERAS-007 will be orally administered in combination with sotorasib to study participants with KRAS G12Cm NSCLC in sequential ascending doses until unacceptable toxicity, disease progression, or withdrawal of consent.
干预措施: ERAS-007 (Drug)
Dose Escalation (Part 2): ERAS-007 plus sotorasib
ERAS-007 will be orally administered in combination with sotorasib to study participants with KRAS G12Cm NSCLC in sequential ascending doses until unacceptable toxicity, disease progression, or withdrawal of consent.
干预措施: Sotorasib (Drug)
Dose Escalation (Part 3): ERAS-601 plus sotorasib
ERAS-601 will be orally administered in combination with sotorasib to study participants with KRAS G12Cm NSCLC in sequential ascending doses until unacceptable toxicity, disease progression, or withdrawal of consent.
干预措施: ERAS-601 (Drug)
Dose Escalation (Part 3): ERAS-601 plus sotorasib
ERAS-601 will be orally administered in combination with sotorasib to study participants with KRAS G12Cm NSCLC in sequential ascending doses until unacceptable toxicity, disease progression, or withdrawal of consent.
干预措施: Sotorasib (Drug)
Dose Expansion (Part 4): ERAS-007 plus osimertinib
ERAS-007 will be orally administered at the recommended dose (as determined from Part 1) in combination with osimertinib to study participants with EGFRm NSCLC.
干预措施: ERAS-007 (Drug)
Dose Expansion (Part 4): ERAS-007 plus osimertinib
ERAS-007 will be orally administered at the recommended dose (as determined from Part 1) in combination with osimertinib to study participants with EGFRm NSCLC.
干预措施: Osimertinib (Drug)
Dose Expansion (Part 5): ERAS-007 plus sotorasib
ERAS-007 will be orally administered at the recommended dose (as determined from Part 2) in combination with sotorasib to study participants with KRAS G12Cm NSCLC.
干预措施: ERAS-007 (Drug)
Dose Expansion (Part 5): ERAS-007 plus sotorasib
ERAS-007 will be orally administered at the recommended dose (as determined from Part 2) in combination with sotorasib to study participants with KRAS G12Cm NSCLC.
干预措施: Sotorasib (Drug)
Dose Expansion (Part 6): ERAS-601 plus sotorasib
ERAS-601 will be orally administered at the recommended dose (as determined from Part 3) in combination with sotorasib to study participants with KRAS G12Cm NSCLC.
干预措施: ERAS-601 (Drug)
Dose Expansion (Part 6): ERAS-601 plus sotorasib
ERAS-601 will be orally administered at the recommended dose (as determined from Part 3) in combination with sotorasib to study participants with KRAS G12Cm NSCLC.
干预措施: Sotorasib (Drug)
结局指标
主要结局
Recommended Dose (RD)
时间窗: Study Day 1 up to Day 22
Based on adverse events observed
Dose Limiting Toxicities (DLT)
时间窗: Study Day 1 up to Day 22
Based on adverse events observed
Maximum Tolerated Dose (MTD)
时间窗: Study Day 1 up to Day 22
Based on adverse events 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
- Plasma concentration (Cmax)(Study Day 1 up to Day 22)
- Time to achieve Cmax (Tmax)(Study Day 1 up to Day 22)
- Half-life(Study Day 1 up to Day 22)
- 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)
- Area under the curve(Study Day 1 up to Day 22)