Sistema de Salut de Catalunya
Institut Català de la Salut
[Van Laethem JL] Gastroenterology, Hepatology and Digestive Oncology, Hopital Universitaire Bruxelles. Erasme Universite Libre de Bruxelles, Brussels, Belgium. [Geboes K] Gastroenterology Department, UZ Gent - University Hospital Ghent, Gent, Belgium. [Borbath I] Hepatogastroenterology, Cliniques Universitaires Saint-Luc (UCLouvain Saint-Luc), Woluwe-Saint-Lambert, Belgium. [Macarulla Mercade T] Medical Oncology Department, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Lambert A] Institut de Cancérologie de Lorraine, Université de Lorraine, Nancy, France. [Cassier P] Medical Oncology Department, Centre Léon Bérard, Lyon, France
Vall d'Hebron Barcelona Hospital Campus
2026-01-27T09:23:09Z
2026-01-27T09:23:09Z
2025-10-21
CD40 agonist; Biomarker; Chemotherapy
Agonista CD40; Biomarcador; Quimioterapia
Agonista CD40; Biomarcador; Quimioteràpia
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).
This study and publication were funded by Alligator Bioscience AB.
Artículo
Versión publicada
Inglés
Pàncrees - Càncer - Tractament; Avaluació de resultats (Assistència sanitària); Anticossos monoclonals - Ús terapèutic; Quimioteràpia combinada; CHEMICALS AND DRUGS::Amino Acids, Peptides, and Proteins::Proteins::Blood Proteins::Immunoproteins::Immunoglobulins::Antibodies::Antibodies, Monoclonal::Antibodies, Monoclonal, Humanized; Other subheadings::Other subheadings::/therapeutic use; ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Therapeutics::Therapeutics::Drug Therapy::Antineoplastic Protocols::Therapeutics::Drug Therapy::Antineoplastic Combined Chemotherapy Protocols; DISEASES::Neoplasms::Neoplasms::Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Pancreatic Neoplasms::Neoplasms::Neoplasms by Site::Carcinoma, Pancreatic Ductal; DISEASES::Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Pancreatic Neoplasms; Other subheadings::Other subheadings::Other subheadings::/drug therapy; ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Diagnosis::Prognosis::Treatment Outcome; COMPUESTOS QUÍMICOS Y DROGAS::aminoácidos, péptidos y proteínas::proteínas::proteínas sanguíneas::inmunoproteínas::inmunoglobulinas::anticuerpos::anticuerpos monoclonales::anticuerpos monoclonales humanizados; Otros calificadores::Otros calificadores::/uso terapéutico; TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::terapéutica::terapéutica::farmacoterapia::protocolos antineoplásicos::terapéutica::farmacoterapia::protocolos de quimioterapia antineoplásica combinada; ENFERMEDADES::neoplasias::neoplasias::neoplasias::neoplasias por localización::neoplasias del sistema digestivo::neoplasias pancreáticas::neoplasias::neoplasias por localización::carcinoma ductal pancreático; ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias del sistema digestivo::neoplasias pancreáticas; Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia; TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::diagnóstico::pronóstico::resultado del tratamiento
Elsevier
Cell Reports Medicine;6(10)
https://doi.org/10.1016/j.xcrm.2025.102407
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
