A Phase 1b/2a Study of Gemcitabine and Nab-paclitaxel in Combination With Avutometinib (VS-6766) and Defactinib in Patients With Previously Untreated Metastatic Adenocarcinoma of the Pancreas
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 40
- 试验地点
- 12
- 主要终点
- To determine the efficacy of the RP2D identified in Part A
研究概览
简要总结
This study will assess the safety and efficacy of avutometinib (VS-6766) and defactinib in combination with gemcitabine and nab-paclitaxel in patients with Pancreatic Ductal Adenocarcinoma (PDAC) who have been previously untreated.
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) and defactinib in combination with gemcitabine and nab-paclitaxel in patients previously untreated metastatic Pancreatic Ductal Adenocarcinoma (PDAC).
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 metastatic pancreatic ductal adenocarcinoma.
- •An Eastern Cooperative Group (ECOG) performance status ≤ 1
- •Measurable disease according to RECIST 1.1
- •Adequate organ function
- •Adequate cardiac function
- •Agreement to use highly effective method of contraceptive
排除标准
- •Patients with pancreatic neuroendocrine tumors
- •Prior or concomitant treatment for metastatic pancreatic ductal adenocarcinoma
- •Prior treatment with inhibitors of the RAS /MAPK pathway [e.g. MEK inhibitors] or inhibitors of FAK
- •History of prior malignancy, with the exception of curatively treated malignancies
- •Major surgery within 4 weeks (excluding placement of vascular access)
- •Concurrent heart disease or severe obstructive pulmonary disease
- •Concurrent ocular disorders
- •Active skin disorder that has required systemic therapy within the past 1 year
- •Patients with interstitial lung disease or pulmonary fibrosis or severe lung disease, pulmonary edema, and adult respiratory distress syndrome
- •Known SARS-Cov2 infection ≤28 days prior to first dose of study therapy
研究组 & 干预措施
Gemcitabine + nab-paclitaxel + avutometinib (VS-6766) + defactinib
To determine the recommended phase 2 dose (RP2D) for gemcitabine Gemcitabine + nab-paclitaxel + avutometinib (VS-6766) + defactinib in patients with untreated metastatic PDAC.
干预措施: avutometinib (VS-6766) and defactinib in combination with gemcitabine and nab-paclitaxel (Drug)
Gemcitabine + nab-paclitaxel + avutometinib (VS-6766) + defactinib RP2D
To determine the efficacy of the RP2D identified in Part A in untreated metastatic PDAC patients
干预措施: avutometinib (VS-6766) and defactinib in combination with gemcitabine and nab-paclitaxel (Drug)
结局指标
主要结局
To determine the efficacy of the RP2D identified in Part A
时间窗: 6 months
Confirmed overall response rate (ORR) (partial response \[PR\] + complete response \[CR\] defined according to Response Evaluation Criteria in Solid Tumors version 1.1 \[RECIST 1.1\])
Part A: To determine RP2D for avutometinib (VS-6766) and defactinib in combination gemcitabine and nab-paclitaxel
时间窗: 28 days
Assessment of Dose-limiting toxicities (DLTs)
次要结局
- Plasma Pharmacokinetics (PK) of avutometinib (VS-6766) and Defactinib and relevant metabolites, Tmax(10 weeks)
- Plasma Pharmacokinetics (PK) of avutometinib (VS-6766) and Defactinib and relevant metabolites, AUC(10 Weeks)
- Number of abnormal laboratory values(24 months)
- Overall Survival (OS)(Up to 5 years)
- Plasma Pharmacokinetics (PK) of avutometinib (VS-6766) and Defactinib and relevant metabolites, Half-life(10 weeks)
- Frequency and severity adverse events (AEs) and Serious Adverse Events (SAEs)(24 months)
- Disease Control Rate (DCR)(24 months)
- Duration of Response (DOR)(24 months)
- Progression Free Survival (PFS)(24 months)