CD40 agonist mitazalimab with mFOLFIRINOX in untreated metastatic pancreatic cancer: Biomarkers associated with outcomes from OPTIMIZE-1.

Fiche publication

Date publication

octobre 2025

Journal

Cell reports. Medicine

Auteurs

Membres identifiés du Cancéropôle Est :
Dr LAMBERT Aurélien

Tous les auteurs :
Van Laethem JL, Geboes K, Borbath I, Macarulla Mercade T, Lambert A, Cassier P, Prenen H, Mitry E, Blanc JF, Pilla L, Feliu J, Rodriguez Garrote M, Pazo-Cid RA, Gallego I, Smith KE, Nordbladh K, Jimenez DG, Ellmark P, Pico de Coaña Y, Ambarkhane SV, Beatty GL, O'Reilly EM

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/41061701

Résumé

Response determinants to immunotherapy in metastatic pancreatic ductal adenocarcinoma (mPDAC) remain unclear, limiting treatment advancements. We report a single-arm phase 1b/2 study (OPTIMIZE-1) evaluating the safety and efficacy of the cluster of differentiation 40 (CD40) agonist mitazalimab combined with modified FOLFIRINOX (mFOLFIRINOX), in chemotherapy-naive patients with mPDAC. Patients receive an initial dose of mitazalimab one week before starting biweekly cycles of mFOLFIRINOX plus mitazalimab. The study meets its pre-specified primary endpoint, achieving a confirmed objective response rate (ORR) of 42.1%. Median duration of response, progression-free survival, and overall survival was 12.6 months, 7.7 months, and 14.9 months, respectively. Multi-omic analyses of tumor and blood specimens identify a baseline tumor-intrinsic gene signature related to fibrosis associated with improved survival. Additionally, mitazalimab-induced increases in activated circulating myeloid, B cell, and T cell frequencies correlate with better outcomes. These results may inform future patient stratification strategies supporting a planned randomized confirmatory trial of mitazalimab with mFOLFIRINOX in mPDAC. This study was registered at ClinicalTrials.gov (NCT04888312).