A Phase 2 Study of Avutometinib (VS-6766) (Dual RAF/MEK Inhibitor) as a Single Agent and In Combination With Defactinib (FAK Inhibitor) in Recurrent KRAS-Mutant (KRAS-MT) and BRAF-Mutant (BRAF-MT) Non-Small Cell Lung Cancer (NSCLC) (RAMP 202)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 90
- 试验地点
- 43
- 主要终点
- To determine the optimal regimen, either avutometinib (VS-6766) monotherapy or avutometinib (VS-6766) in combination with defactinib, in KRAS-G12V NSCLC
研究概览
简要总结
This study will assess the safety and efficacy of avutometinib (VS-6766) monotherapy or VS-6766 in combination with defactinib in subjects with recurrent Non-small cell lung cancer.
详细描述
This is a multicenter, open-label Phase 2 study designed to evaluate safety and tolerability and efficacy of avutometinib (VS-6766) versus avutometinib (VS-6766) in combination with defactinib in subjects with KRAS and BRAF mutant NSCLC following treatment with an appropriate platinum-based regimen and an approved immune checkpoint inhibitor (CPI).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female subjects ≥ 18 years of age
- •Histologic or cytologic evidence of NSCLC
- •Known KRAS or BRAF mutation
- •The subject must have received appropriate prior therapy
- •Measurable disease according to RECIST 1.1
- •An Eastern Cooperative Group (ECOG) performance status ≤ 1
- •Adequate organ function
- •Adequate recovery from toxicities related to prior treatments
- •Agreement to use highly effective method of contraceptive
排除标准
- •Systemic anti-cancer therapy within 4 weeks of the first dose of study therapy
- •History of prior malignancy, with the exception of curatively treated malignancies
- •Major surgery within 4 weeks (excluding placement of vascular access)
- •History of treatment with a direct and specific inhibitor of MEK, KRAS or BRAF except for treatment of BRAF V-600E mutant NSCLC
- •Exposure to strong CYP2C9 and CYP3A4 inhibitors or inducers within 7 days prior to the first dose and during the course of therapy
- •Symptomatic brain metastases requiring steroids or other local interventions.
- •Known SARS-Cov2 infection ≤28 days prior to first dose of study therapy
- •Active skin disorder that has required systemic therapy within the past 1 year
- •History of rhabdomyolysis
- •Concurrent ocular disorders
- •Concurrent heart disease or severe obstructive pulmonary disease
- •Subjects with the inability to swallow oral medications
研究组 & 干预措施
Arm 1: avutometinib (VS-6766) monotherapy
in patients with NSCLC KRAS-G12V tumor
干预措施: avutometinib (VS-6766) (Drug)
Arm 2: avutometinib (VS-6766) in combination with defactinib
in patients with a NSCLC KRAS-G12V tumor
干预措施: avutometinib (VS-6766) and Defactinib (Drug)
Arm 3: avutometinib (VS-6766) in combination with defactinib
in patients with a NSCLC KRAS-other (non-G12V) tumor
干预措施: avutometinib (VS-6766) and Defactinib (Drug)
Arm 4: avutometinib (VS-6766) in combination with defactinib
in patients with a NSCLC BRAF-V600E tumor
干预措施: avutometinib (VS-6766) and Defactinib (Drug)
Arm 5:avutometinib (VS-6766) in combination with defactinib
in patients with a NSCLC BRAF-non-V600E tumor
干预措施: avutometinib (VS-6766) and Defactinib (Drug)
结局指标
主要结局
To determine the optimal regimen, either avutometinib (VS-6766) monotherapy or avutometinib (VS-6766) in combination with defactinib, in KRAS-G12V NSCLC
时间窗: From start of treatment to confirmation of response; 24 weeks
Confirmed overall response rate per RECIST 1.1
To evaluate the initial efficacy of avutometinib (VS-6766) in combination with defactinib in BRAF-MT NSCLC
时间窗: From start of treatment to confirmation of response; 24 weeks
Confirmed overall response rate per RECIST 1.1
To determine efficacy in KRAS-other (non-G12V) NSCLC
时间窗: From start of treatment to confirmation of response; 24 weeks
Confirmed overall response rate per RECIST 1.1
To determine the efficacy of avutometinib (VS-6766) in combination with defactinib in BRAF-MT NSCLC
时间窗: From start of treatment to confirmation of response; 24 weeks
Confirmed overall response rate per RECIST 1.1
次要结局
- Overall Survival (OS)(Up to 5 years)
- To characterize the safety and toxicity profile of VS-6766 as a monotherapy and in combination with defactinib in KRAS-MT NSCLC and in BRAF-MT NSCLC(24 weeks)
- Overall Response Rate per RECIST 1.1 as assessed by Investigator(From start of treatment to confirmation of response; 24 weeks)
- Duration of Response (DOR)(Time from the first documentation of response to first documentation of progressive disease or death due to any cause, greater than or equal to 6 months)
- Disease Control Rate (DCR)(Greater than or equal to 8 weeks)
- Progression Free Survival (PFS)(Up to 5 years)