Background: Increased platelet-derived growth factor receptor alpha (PDGFRα) expression is linked to epithelial-mesenchymal transition in pancreatic cancer. Olaratumab (O) is a fully human monoclonal antibody against PDGFRα previously approved for the treatment of advanced soft tissue sarcoma. Here, we report the initial safety and antitumor activity data of O in combination with nab-paclitaxel + gemcitabine (nPG) in first-line metastatic pancreatic cancer patients (pts). Methods: In this 3+3 dose escalation study, pts with stage IV pancreatic cancer received intravenous 15 mg/kg (cohort 1) or 20 mg/kg (cohort 2) O + nPG (125 mg/m²/1000 mg/m²) on D1, 8, and 15 of a 28-day cycle. Following dose escalation, additional pts were enrolled in an expansion phase to confirm safety. Primary objective was to determine a dose of O that can be safely combined with nPG. Results: As of September 2018, 10 pts were treated in dose escalation (cohort 1: 3 pts; cohort 2: 7 pts) with no dose-limiting toxicities (DLTs) observed. Safety of 20 mg/kg O + nPG was confirmed in the expansion cohort; 1 of 12 pts (8.3%) experienced a DLT of grade 4 neutropenia. Most frequent adverse events (AEs) (≥ 25%) reported across all cohorts included fatigue (50%); neutropenia (50%); nausea (46%); thrombocytopenia (41%); and constipation (32%). Related grade ≥ 3 AEs reported in > 2 pts were neutropenia (N = 7; 32%), infusion-related reaction, and neuropathy (both N = 3; 14%). There were no deaths related to study drugs. Among pts evaluable for response, 2 of 15 pts had a partial response and 11 pts had stable disease as best response for an objective response rate of 13%. Notably, 2 of 3 pts in cohort 1 continue on treatment for more than 12 months as of the data cut-off. Updated data will be presented at the meeting. Conclusions: Both dose levels were tolerated. Safety profile was similar to nPG chemotherapy with most toxicity manageable through dose adjustments of nPG. Clinical trial information: NCT03086369