1Globe Health Institute

4110 Background: NAPA is an oral investigational agent, hypothesized to inhibit cancer stemness pathways, including STAT3 pathway implicated in cancer stem-cell viability. We report updated data in a study of mPDAC patients (pts) (NCT02231723) treated with NAPA + nPTX + Gem, including a subgroup of pts eligible for enrollment in the ongoing phase 3 study (NCT02993731, CanStem111P). Methods: A phase 1b/2 multicenter study in mPDAC pts was done to assess the recommended phase 2 dose, PK profile, and signals of anticancer activity of NAPA + nPTX + Gem. Pts received NAPA 240 mg BID + weekly nPTX 125 mg/m2 + Gem 1000 mg/m2 for 3 of every 4 weeks until disease progression or other discontinuation criteria. Results: Of 59 study pts, 47 (79.7%) were treatment-naïve, and 12 (20.3%) had prior adjuvant treatment. There were no notable PK interactions or dose-limiting toxicities. The most common adverse events included grade 1 diarrhea, neuropathy, pyrexia, and grades 1/2 nausea and fatigue. Among all 59 pts, disease control rate (DCR) was observed in 46 (78.0%) with 2 complete responses (CR) (3.4%) and 26 partial responses (PR) (44.1%) with maturing median progression-free survival (mPFS) and overall survival (mOS) of 7.06 and 9.59 mo, respectively. Among the 50 evaluable pts by RECIST, DCR was 92.0%, with 2 CR (4.0%) and 26 PR (52.0%). Of 9 nonevaluable pts, treatment stopped due to disease progression (3), death (1), noncompliance (2), pt withdrawal (2), and insurance coverage loss (1). In 29 pts eligible for CanStem111P trial, mPFS and mOS is 7.10 and 12.62 mo, respectively. Clinical trial information: NCT02231723. ORR, objective response rate; N/A, not yet reached 1Evaluable: received ≥1 dose of study drug and had ≥1 on-study RECIST evaluation Conclusions: NAPA was well tolerated when combined with nPTX + Gem, with encouraging signs of activity in mPDAC, which are now being further investigated in an ongoing phase 3 study. Subset DCR % ORR % 1 yr OS rate (95% CI) 2 yr OS rate (95% CI) Evaluable1 All Evaluable All All 92.0 78.0 56.0 47.5 46 (33,58) 13 (5,25) Pts eligible for CanStem111P 88.5 79.3 53.8 48.3 54 (34,70) N/A