Universidad Peruana Cayetano Heredia

A Phase I-II multicenter trial with Avelumab plus autologous dendritic cell vaccine in pre-treated mismatch repair-proficient (MSS) metastatic colorectal cancer patients; GEMCAD 1602 study

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dc.contributor.author Espanol-Rego, Marta
dc.contributor.author Fernandez-Martos, Carlos
dc.contributor.author Elez, Elena
dc.contributor.author Foguet, Carles
dc.contributor.author Pedrosa, Leire
dc.contributor.author Rodriguez, Nuria
dc.contributor.author Ruiz-Casado, Ana
dc.contributor.author Pineda, Estela
dc.contributor.author Cid, Joan
dc.contributor.author Cabezon, Raquel
dc.contributor.author Oliveres, Helena
dc.contributor.author Lozano, Miquel
dc.contributor.author Gines, Angels
dc.contributor.author Garcia-Criado, Angeles
dc.contributor.author Ayuso, Juan Ramon
dc.contributor.author Pages, Mario
dc.contributor.author Cuatrecasas, Miriam
dc.contributor.author Torres, Ferran
dc.contributor.author Thomson Okatsu, Timothy M.
dc.contributor.author Cascante, Marta
dc.contributor.author Benitez-Ribas, Daniel
dc.contributor.author Maurel, Joan
dc.date.accessioned 2022-10-12T18:25:57Z
dc.date.available 2022-10-12T18:25:57Z
dc.date.issued 2022
dc.identifier.uri https://hdl.handle.net/20.500.12866/12367
dc.description.abstract Background: Immune check-point blockade (ICB) has shown clinical benefit in mismatch repair-deficient/microsatellite instability high metastatic colorectal cancer (mCRC) but not in mismatch repair-proficient/microsatellite stable patients. Cancer vaccines with autologous dendritic cells (ADC) could be a complementary therapeutic approach to ICB as this combination has the potential to achieve synergistic effects. Methods: This was a Phase I/II multicentric study with translational sub-studies, to evaluate the safety, pharmacodynamics and anti-tumor effects of Avelumab plus ADC vaccine in heavily pre-treated MSS mCRC patients. Primary objective was to determine the maximum tolerated dose and the efficacy of the combination. The primary end-point was 40% progression-free survival at 6 months with a 2 Simon Stage. Results: A total of 28 patients were screened and 19 pts were included. Combined therapy was safe and well tolerated. An interim analysis (Simon design first-stage) recommended early termination because only 2/19 (11%) patients were disease free at 6 months. Median PFS was 3.1 months [2.1–5.3 months] and overall survival was 12.2 months [3.2–23.2 months]. Stimulation of immune system was observed in vitro but not clinically. The evaluation of basal RNA-seq noted significant changes between pre and post-therapy liver biopsies related to lipid metabolism and transport, inflammation and oxidative stress pathways. Conclusions: The combination of Avelumab plus ADC vaccine is safe and well tolerated but exhibited modest clinical activity. Our study describes, for the first-time, a de novo post-therapy metabolic rewiring, that could represent novel immunotherapy-induced tumor vulnerabilities. en_US
dc.language.iso eng
dc.publisher Springer
dc.relation.ispartofseries Cancer Immunology, Immunotherapy
dc.rights info:eu-repo/semantics/restrictedAccess
dc.rights.uri https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
dc.subject Vaccines en_US
dc.subject Metabolism en_US
dc.subject Resistance en_US
dc.title A Phase I-II multicenter trial with Avelumab plus autologous dendritic cell vaccine in pre-treated mismatch repair-proficient (MSS) metastatic colorectal cancer patients; GEMCAD 1602 study en_US
dc.type info:eu-repo/semantics/article
dc.identifier.doi https://doi.org/10.1007/s00262-022-03283-5
dc.relation.issn 1432-0851


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