Background: 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). 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. Results: The dose escalation cohort has been completed with a total of 20 patients with refractory solid tumors. The common treatment-related adverse events included nausea (50%), vomiting (40%), diarrhea (35%), anorexia (30%), fever (25%), and myalgia (25%). No DLTs were observed, therefore the Level 5 dose was deemed to be the RP2D. Among the 15 patients evaluable for treatment response, 1 (7%) partial response, 8 (53%) stable disease and 6 (40%) disease progression were observed. The median time on treatment was 132 days for all evaluable patients, and 127 days in the 8 PDAC patients with the longest time on treatment being 290 days. Partial response was seen in a patient with PDAC who progressed on gemcitabine and nab-paclitaxel. Paired biopsies in PDAC patients showed increased proliferating CD8+ T cells and decreased macrophages with treatment. Conclusions: The combination regimen is well tolerated. Dose Level 5 is the RP2D dose. The expansion cohort (PDAC only) is ongoing. Efficacy and correlative data is forthcoming. Clinical trial information: 02546531.