Cell reports. Medicine · 2025
CD40 agonist mitazalimab with mFOLFIRINOX in untreated metastatic pancreatic cancer: Biomarkers associated with outcomes from OPTIMIZE-1.
СтатьяКлиническое исследование II фазыКлиническое исследование I фазыНазвание и аннотация: Перевод в очереди
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Van Laethem Jean-Luc, Geboes Karen, Borbath Ivan, Macarulla Mercade Teresa, Lambert Aurélien, Cassier Philippe, Prenen Hans, Mitry Emmanuel, Blanc Jean-Frédéric, Pilla Lorenzo, Feliu Jaime, Rodriguez Garrote Mercedes, Pazo-Cid Roberto Antonio, Gallego Inmaculada, Smith Karin Enell, Nordbladh Karin, Jimenez David Gomez, Ellmark Peter, Pico de Coaña Yago, Ambarkhane Sumeet Vijay, Beatty Gregory L, O'Reilly Eileen M
Аннотация
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).