Study of Avutometinib (VS-6766) +Defactinib With Gemcitabine and Nab-paclitaxel in Patients With Pancreatic Cancer

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