HCQ (autophagy inhibitor) + CPC (AKT/EMT-modulating repurposed agent) added to mFOLFIRINOX delivers 39% ORR in 1L advanced PDAC

Hydroxychloroquine (HCQ), a lysosomotropic autophagy inhibitor, and chlorphenesin carbamate (CPC), a repurposed agent proposed to blunt AKT-mediated EMT, were combined with first-line modified FOLFIRINOX in a multicenter, single-arm Phase 2 study in Korea (NCT05083780) enrolling locally advanced unresectable or metastatic PDAC (treated n=40; efficacy set n=39). Key outcomes were ORR 39% (15/39) with disease control 92.3% (36/39), median PFS 7.4 months (95% CI, 6.2–13.3) and median OS 14.8 months (95% CI, 9.6–27.9); by subgroup, OS was 20.5 months in locally advanced vs 13.9 months in metastatic disease, with 13% conversion to curative-intent surgery (5/40). Grade 3–4 AEs were largely mFOLFIRINOX-typical (neutropenia 40%, nausea 13%, anemia 10%)—efficacy looks broadly in-family with historical first-line FOLFIRINOX in metastatic PDAC (median OS ~11.1 months in PRODIGE/ACCORD) rather than a clear step-change, but the OS signal in locally advanced disease sits in the range reported with FOLFIRINOX-based approaches (often ~18–24 months, regimen- and selection-dependent).