Single-arm phase 1b/2 trial evaluates mitazalimab's efficacy in untreated metastatic pancreatic cancer, suggesting implications for future treatment strategies.
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).
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Laethem et al. (2025) studied this question.
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