Background: nal-IRI+5-FU/LV is effective for patients with mPAC after disease progression following gemcitabine-based therapy. The current study (NCT02551991) is a phase 1/2, open-label trial to assess the safety, tolerability, and dose-limiting toxicities (DLT) of nal-IRI+5-FU/LV+OX (NAPOX) for the first-line treatment of patients with mPAC and to determine Phase 3 dosing. Methods: NAPOX is being evaluated in patients ≥18 yrs with previously untreated mPAC, with an ECOG performance status ≤1 and adequate organ function. Three of 4 dose-escalation cohorts of NAPOX, dosed on day 1 and 15, have been initiated. Safety and tolerability are the primary endpoints of this study, with assessment of exploratory efficacy signals. Results: As of 10 Nov 2017, 24 patients (Cohort A: n = 7; Cohort B: n = 7; Cohort C: n = 10) have received ≥1 dose of NAPOX (median age: 66.0 yrs, range: 44–78 yrs). Five patients reported ≥1 DLT (Cohort A: n = 2/7; Cohort B: n = 1/7; Cohort C: n = 2/10). The most frequent treatment-emergent adverse events (TEAEs) were gastrointestinal (GI) disorders (Cohort A: 71%; Cohort B: 71%; Cohort C: 60%). Grade 3 or 4 TEAEs were GI disorders (Cohort A; 43%; Cohort B: 14%; Cohort C: 50%) and neutropenia (Cohort A: 43%; Cohort B: 29%; Cohort C: 40%). The best overall response was partial response (PR) in 6/24 patients (Cohort B: n = 3/7; Cohort C: n = 3/10). In Cohort B (the lowest and most tolerable cohort), n = 5/7 patients reached disease control (PR or stable disease > 16 weeks), with n = 4/7 patients were treated for ≥24 weeks. Conclusions: Initial analysis suggests a well-tolerated dose and promising antitumor clinical activity of NAPOX. Dose escalation and expansion is ongoing. Clinical trial information: NCT02551991

* Cohort not yet initiated