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DC Field | Value | Language |
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dc.contributor.author | Simonelli, M. | - |
dc.contributor.author | Garralda, E. | - |
dc.contributor.author | Eskens, Ferry | - |
dc.contributor.author | Gil Martin, M. | - |
dc.contributor.author | Yen, C. J. | - |
dc.contributor.author | Obermannova, R. | - |
dc.contributor.author | Chao, Y. | - |
dc.contributor.author | Lonardi, S. | - |
dc.contributor.author | Melichar, B. | - |
dc.contributor.author | Moreno, V. | - |
dc.contributor.author | Yu, M. L. | - |
dc.contributor.author | Bongiovanni, A. | - |
dc.contributor.author | Calvo, E. | - |
dc.contributor.author | Rottey, S. | - |
dc.contributor.author | Machiels, J. P. | - |
dc.contributor.author | Gonzalez Martin, A. | - |
dc.contributor.author | Paz Ares, L. | - |
dc.contributor.author | Chang, C. L. | - |
dc.contributor.author | Mason, W. | - |
dc.contributor.author | Lin, C. C. | - |
dc.contributor.author | Reardon, D. A. | - |
dc.contributor.author | Vieito, M. | - |
dc.contributor.author | Santoro, A. | - |
dc.contributor.author | Meng, R. | - |
dc.contributor.author | Abbadessa, G. | - |
dc.contributor.author | Menas, F. | - |
dc.contributor.author | Lee, H. | - |
dc.contributor.author | Liu, Q. | - |
dc.contributor.author | Combeau, C. | - |
dc.contributor.author | Ternes, N. | - |
dc.contributor.author | Ziti Ljajic, S. | - |
dc.contributor.author | Massard, C. | - |
dc.date.accessioned | 2022-10-25T14:25:34Z | - |
dc.date.available | 2022-10-25T14:25:34Z | - |
dc.date.issued | 2022-10-01 | - |
dc.identifier.issn | 2059-7029 | - |
dc.identifier.uri | http://hdl.handle.net/2445/190195 | - |
dc.description.abstract | Background: The anti-CD38 antibody isatuximab is approved for the treatment of relapsed/refractory multiple myeloma, but there are no data on its efficacy in solid tumors. This phase I/II study (NCT03637764) assessed the safety and activity of isatuximab plus atezolizumab (Isa + Atezo), an anti-programmed death-ligand 1 (PD-L1) antibody, in patients with immunotherapy-naive solid tumors: epithelial ovarian cancer (EOC), glioblastoma (GBM), hepatocellular carcinoma (HCC), and squamous cell carcinoma of the head and neck (SCCHN). Patients and methods: Phase I assessed safety, tolerability, pharmacokinetics, pharmacodynamics, and the recommended phase II dose (RP2D) of isatuximab 10 mg/kg intravenously (i.v.) every week for 3 weeks followed by once every 3 weeks + atezolizumab 1200 mg i.v. every 3 weeks. Phase II used a Simon's two-stage design to assess the overall response rate or progression-free survival rate at 6 months (GBM cohort). Interim analysis was carried out at 6 months following first dose of the last enrolled patient in each cohort. Pharmacodynamic biomarkers were tested for CD38, PD-L1, tumor-infiltrating immune cells, and FOXP3+ regulatory T cells (Tregs) in the tumor microenvironment (TME). Results: Overall, 107 patients were treated (EOC, n = 18; GBM, n = 33; HCC, n = 27; SCCHN, n = 29). In phase I, Isa + Atezo showed an acceptable safety profile, no dose-limiting toxicities were observed, and RP2D was confirmed. Most patients experienced >= 1 treatment-emergent adverse event (TEAE), with <= 48.5% being grade >= 3. The most frequent TEAE was infusion reactions. The study did not continue to stage 2 based on prespecified targets. Tumor-infiltrating CD38+ immune cells were reduced and almost cleared after treatment. Isa + Atezo did not significantly modulate Tregs or PD-L1 expression in the TME. Conclusions: Isa + Atezo had acceptable safety and tolerability. Clinical pharmacodynamic evaluation revealed efficient target engagement of isatuximab via treatment-mediated reduction of CD38+ immune cells in the TME. Based on clinical data, CD38 inhibition does not improve responsiveness to PD-L1 blockade in these patients. | - |
dc.format.extent | 8 p. | - |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | Elsevier BV | - |
dc.relation.isformatof | Reproducció del document publicat a: https://doi.org/10.1016/j.esmoop.2022.100562 | - |
dc.relation.ispartof | ESMO Open, 2022, vol. 7, issue. 5, p. 100562 | - |
dc.relation.uri | https://doi.org/10.1016/j.esmoop.2022.100562 | - |
dc.rights | cc by (c) Simonelli, M. et al., 2022 | - |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/es/ | * |
dc.source | Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) | - |
dc.subject.classification | Tumors | - |
dc.subject.classification | Càncer de fetge | - |
dc.subject.other | Tumors | - |
dc.subject.other | Liver cancer | - |
dc.title | Isatuximab plus atezolizumab in patients with advanced solid tumors: results from a phase I/II, open-label, multicenter study | - |
dc.type | info:eu-repo/semantics/article | - |
dc.type | info:eu-repo/semantics/publishedVersion | - |
dc.date.updated | 2022-10-20T08:48:10Z | - |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | - |
dc.identifier.pmid | 35987165 | - |
Appears in Collections: | Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
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PIIS2059702922001909.pdf | 393.09 kB | Adobe PDF | View/Open |
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