dc.contributor
Institut Català de la Salut
dc.contributor
[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
dc.contributor
Vall d'Hebron Barcelona Hospital Campus
dc.contributor.author
Van Laethem, Jean-Luc
dc.contributor.author
Geboes, Karen
dc.contributor.author
Borbath, Ivan
dc.contributor.author
Lambert, Aurélien
dc.contributor.author
Macarulla, Teresa
dc.contributor.author
CASSIER, Philippe
dc.date.accessioned
2026-01-28T01:40:46Z
dc.date.available
2026-01-28T01:40:46Z
dc.date.issued
2026-01-27T09:23:09Z
dc.date.issued
2026-01-27T09:23:09Z
dc.date.issued
2025-10-21
dc.identifier
Van Laethem JL, Geboes K, Borbath I, Macarulla Mercade T, Lambert A, Cassier P, et al. CD40 agonist mitazalimab with mFOLFIRINOX in untreated metastatic pancreatic cancer: Biomarkers associated with outcomes from OPTIMIZE-1. Cell Reports Med. 2025 Oct 21;6(10):102407.
dc.identifier
http://hdl.handle.net/11351/14191
dc.identifier
10.1016/j.xcrm.2025.102407
dc.identifier
001605972100019
dc.identifier.uri
http://hdl.handle.net/11351/14191
dc.description.abstract
CD40 agonist; Biomarker; Chemotherapy
dc.description.abstract
Agonista CD40; Biomarcador; Quimioterapia
dc.description.abstract
Agonista CD40; Biomarcador; Quimioteràpia
dc.description.abstract
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).
dc.description.abstract
This study and publication were funded by Alligator Bioscience AB.
dc.format
application/pdf
dc.relation
Cell Reports Medicine;6(10)
dc.relation
https://doi.org/10.1016/j.xcrm.2025.102407
dc.rights
Attribution 4.0 International
dc.rights
http://creativecommons.org/licenses/by/4.0/
dc.rights
info:eu-repo/semantics/openAccess
dc.subject
Pàncrees - Càncer - Tractament
dc.subject
Avaluació de resultats (Assistència sanitària)
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Anticossos monoclonals - Ús terapèutic
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Quimioteràpia combinada
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CHEMICALS AND DRUGS::Amino Acids, Peptides, and Proteins::Proteins::Blood Proteins::Immunoproteins::Immunoglobulins::Antibodies::Antibodies, Monoclonal::Antibodies, Monoclonal, Humanized
dc.subject
Other subheadings::Other subheadings::/therapeutic use
dc.subject
ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Therapeutics::Therapeutics::Drug Therapy::Antineoplastic Protocols::Therapeutics::Drug Therapy::Antineoplastic Combined Chemotherapy Protocols
dc.subject
DISEASES::Neoplasms::Neoplasms::Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Pancreatic Neoplasms::Neoplasms::Neoplasms by Site::Carcinoma, Pancreatic Ductal
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DISEASES::Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Pancreatic Neoplasms
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Other subheadings::Other subheadings::Other subheadings::/drug therapy
dc.subject
ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Diagnosis::Prognosis::Treatment Outcome
dc.subject
COMPUESTOS QUÍMICOS Y DROGAS::aminoácidos, péptidos y proteínas::proteínas::proteínas sanguíneas::inmunoproteínas::inmunoglobulinas::anticuerpos::anticuerpos monoclonales::anticuerpos monoclonales humanizados
dc.subject
Otros calificadores::Otros calificadores::/uso terapéutico
dc.subject
TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::terapéutica::terapéutica::farmacoterapia::protocolos antineoplásicos::terapéutica::farmacoterapia::protocolos de quimioterapia antineoplásica combinada
dc.subject
ENFERMEDADES::neoplasias::neoplasias::neoplasias::neoplasias por localización::neoplasias del sistema digestivo::neoplasias pancreáticas::neoplasias::neoplasias por localización::carcinoma ductal pancreático
dc.subject
ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias del sistema digestivo::neoplasias pancreáticas
dc.subject
Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia
dc.subject
TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::diagnóstico::pronóstico::resultado del tratamiento
dc.title
CD40 agonist mitazalimab with mFOLFIRINOX in untreated metastatic pancreatic cancer: Biomarkers associated with outcomes from OPTIMIZE-1
dc.type
info:eu-repo/semantics/article
dc.type
info:eu-repo/semantics/publishedVersion
