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