Atebimetinib (MEK deep cyclic inhibitor) + mGnP Delivers 42% ORR in 1L Metastatic PDAC

Atebimetinib is an oral next-generation MEK “deep cyclic inhibitor” (DCI) designed for pulsatile MAPK-pathway inhibition, and was combined with modified gemcitabine/nab-paclitaxel (mGnP; every-other-week dosing) in a multicenter, open-label, nonrandomized Phase 2a first-line advanced/metastatic PDAC cohort (NCT05585320). Among 55 treated patients (50 response-evaluable; ECOG 0–1), investigator-assessed ORR was 42% (21/50 PR) with DCR 84%, median PFS 8.3 months, and 6- and 9-month OS rates of 88% and 79% (median OS not reached; median follow-up 10.4 months; cutoff January 7, 2026)—numerically above historical weekly GnP in MPACT (ORR ~23%, median PFS ~5.5 months, median OS ~8.5 months). No Grade 5 TRAEs were reported; no atebimetinib-related AE exceeded Grade 3, with Grade 3 atebimetinib-related AEs in 29% (most commonly rash 5%, ALT 5%, AST 5%), which reads as potentially “chemo-compatible” for a MEK-pathway approach where tolerability has often limited dosing.