Overview
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.
Description
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).
Eligibility
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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