NP137 (anti–netrin-1; EMT inhibitor) + mFOLFIRINOX Delivers 10.9-mo mPFS in 1L Locally Advanced PDAC

NP137 is a monoclonal antibody that neutralizes netrin-1 to inhibit epithelial-to-mesenchymal transition (EMT), combined here with modified FOLFIRINOX as first-line therapy in LAPNET-01, a single-arm Phase Ib study in treatment-naïve, locally advanced unresectable PDAC (n=43; NCT06203821). At a 6-month safety landmark, AEs occurred in 100% with 58% Grade ≥3; efficacy readouts included ORR 29% with disease control 95%, median PFS 10.9 months (95% CI, 10.0–15.6), median OS 16.4 months (95% CI, 12.8–NR), and surgical conversion in 23%—broadly in the range of published mFOLFIRINOX benchmarks in LAPC (mPFS ≈10.6 months; mOS ≈18.1 months) and similar to reported conversion-to-surgery rates across heterogeneous series (pooled ≈26%). Translationally, microbulk RNA-seq showed EMT pathway downregulation on-treatment; baseline high neogenin (NEO1) expression correlated with longer mPFS (15.7 vs 10.2 months, p=0.01) and mOS (NR vs 16.5 months, p=0.024), positioning NEO1 as an enrichment biomarker hypothesis.