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| Home > Articles > Published articles > 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 |
| Home > Articles > Published articles > 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 |
(Hospital Clínic i Provincial de Barcelona) (Vall d'Hebron Institut d'Oncologia) (Hospital Clínic i Provincial de Barcelona) (Hospital Clínic i Provincial de Barcelona) (Hospital Clínic i Provincial de Barcelona) (Hospital Clínic i Provincial de Barcelona) (Hospital Clínic i Provincial de Barcelona) (Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas) (Hospital Clínic i Provincial de Barcelona)| Date: | 2022 |
| Abstract: | 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. 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. 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. 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. The online version contains supplementary material available at 10. 1007/s00262-022-03283-5. |
| Grants: | Instituto de Salud Carlos III PI17/00732 Ministerio de Economía, Industria y Competitividad PI13/01728 Instituto de Salud Carlos III PI19/00740 Agencia Estatal de Investigación PID2020-115051RB-I00 Agència de Gestió d'Ajuts Universitaris i de Recerca 2014SGR474 Agència de Gestió d'Ajuts Universitaris i de Recerca 2017SGR1174 Agència de Gestió d'Ajuts Universitaris i de Recerca 2017SGR1033 Fundació la Marató de TV3 201330.10 |
| Rights: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.  |
| Language: | Anglès |
| Document: | Article ; recerca ; Versió publicada |
| Subject: | Vaccines ; Metabolism ; Resistance |
| Published in: | Cancer Immunology, Immunotherapy, Vol. 72 (september 2022) , p. 827-840, ISSN 1432-0851 |
