A Phase 1/2 Study of Avutometinib (VS-6766) in Combination With Adagrasib in Patients With KRAS G12C Mutant Non-Small Cell Lung Cancer (NSCLC) (RAMP 204)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 12
- 试验地点
- 13
- 主要终点
- Part A: To determine RP2D for avutometinib(VS-6766) in combination with adagrasib
研究概览
简要总结
This study will assess the safety and efficacy of avutometinib (VS-6766) in combination with adagrasib in patients with G12C Non-Small Cell Lung Cancer (NSCLC) who have been exposed to prior G12C inhibitor and experienced progressive disease.
详细描述
This is a multicenter, non-randomized, open-label Phase 1/2 study designed to evaluate safety, tolerability and efficacy of avutometinib (VS-6766) in combination with adagrasib in patients with KRAS G12C mutant NSCLC who have been exposed to prior G12C inhibitor and experienced progressive disease.
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 —（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 G12C mutation
- •The subject must have received prior therapy with a KRAS G12C inhibitor and experienced progression
- •Must have received appropriate treatment with at least one prior systemic regimen, but no more than 3 prior regimens, for Stage 3B-C or 4 NSCLC
- •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
- •Prior chemotherapy, targeted therapies, radiotherapy, immunotherapy or treatment with an investigational agent within 14 days of receipt of study drug (within 6 weeks for nitrosoureas, mitomycin C and chest radiation; within 6 months prior to Cycle 1 Day 1 for chest radiation > 30Gy)
- •History of prior malignancy, with the exception of curatively treated malignancies
- •Major surgery within 4 weeks (excluding placement of vascular access)
- •Exposure to strong CYP3A4 inhibitors or inducers within 14 days prior to the first dose and during the course of therapy
- •Exposure to strong inhibitors of breast cancer resistance protein (BCRP) within 14 days prior to the first dose and during the course of therapy
- •Symptomatic brain metastases requiring steroids or other local interventions within the 2 weeks prior to initiation of therapy
- •Known SARS-Cov2 infection ≤28 days prior to first dose of study therapy
- •Known hepatitis B, hepatitis C, or human immunodeficiency virus infection that is active
- •Active skin disorder that has required systemic therapy within the past 1 year
- •History of rhabdomyolysis or interstitial lung disease
- •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
avutometinib(VS-6766)+adagrasib
To determine the recommended phase 2 dose (RP2D) for VS-6766 in combination with adagrasib in G12C inhibitor exposed patients
干预措施: avutometinib (VS-6766) and adagrasib (Drug)
avutometinib (VS-6766)+adagrasib RP2D
To determine the efficacy of the RP2D identified from Part A in G12C inhibitor exposed patients
干预措施: avutometinib (VS-6766) and adagrasib (Drug)
结局指标
主要结局
Part A: To determine RP2D for avutometinib(VS-6766) in combination with adagrasib
时间窗: From start of treatment to confirmation of RP2D; 28 days
Assessment of Dose-limiting toxicities (DLTs)
To determine the efficacy of the optimal regimen identified from Part A
时间窗: From start of treatment to confirmation of response; 16 weeks
Confirmed overall response rate per RECIST 1.1
次要结局
- ECG QT Interval(24 months)
- 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)
- To characterize the safety and toxicity profile:(24 Months)
- Plasma Pharmacokinetics (PK) of avutometinib(VS 6766), adagrasib, and relevant metabolites - Tmax(10 weeks)
- Disease Control Rate (DCR)(Greater than or equal to 8 weeks)
- Progression Free Survival (PFS)(24 months)
- Overall Survival (OS)(Up to 5 years)
- Plasma Pharmacokinetics (PK) of avutometinib(VS 6766), adagrasib, and relevant metabolites - AUC(10 weeks)
- Plasma Pharmacokinetics (PK) of avutometinib(VS 6766), adagrasib, and relevant metabolites - Half-life(10 weeks)
- Clinical Benefit Rate(≥ 6 months)