Phase I Study Of Defactinib Combined With Pembrolizumab And Gemcitabine In Patients With Advanced Cancer.

380Background: Focal adhesion kinase (FAK) is consistently hyperactivated in multiple tumor types including pancreatic ductal adenocarcinoma (PDAC). Our preclinical work showed that FAK and PD-1 inhibitors elicit significant tumor regression, and a maximal response is achieved by combining FAK and PD-1 inhibitors with gemcitabine, suggesting the need for a cytotoxic agent to bolster antigen presentation (Jiang H et al, Nature Medicine 2016). Defactinib is an orally available, well-tolerated, potent ATP-competitive FAK inhibitor. Methods: Eligible patients are being treated according to the dose escalation schema (Table 1). A 3+3 design is being used. The study has an expansion portion for PDAC patients at the recommended phase 2 dose (RP2D). The primary endpoint is to determine the RP2D. Secondary endpoints include safety, toxicity, objective response rate, progression-free survival and overall survival. The exploratory endpoints include developing a molecular and immune profile for treatment response. Re...