2026-04-14T03:56:05Zhttps://recercat.cat/oai/request

oai:recercat.cat:11351/95252024-12-13T11:11:56Zcom_2072_378070com_2072_378040col_2072_378092

A phase 1/2, open-label, multicenter study of isatuximab in combination with cemiplimab in patients with lymphoma Carlo-Stella, Carmelo ZINZANI, PIER LUIGI Sureda, Anna Araújo, Luis Casasnovas, René-Olivier Cecilia del Carmen, Carpio Segura Institut Català de la Salut [Carlo-Stella C] Department of Biomedical Sciences, Humanitas University and Department of Oncology and Hematology, IRCCS Humanitas Research Hospital, Milano, Italy. [Zinzani PL] IRCCS Azienda Ospedaliero‐Universitaria di Bologna Istituto di Ematologia “Seràgnoli” and Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale Università di Bologna, Bologna, Italy. [Sureda A] Institut Català D'Oncologia ‐ Hospital Duran i Reynals, IDIBELL, Universitat de Barcelona, Barcelona, Spain. [Araújo L] Universitário de Coimbra, Coimbra, Portugal. [Casasnovas O] Hématologie Clinique, CHU Dijon Bourgogne, Dijon, France. [Carpio C] Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain. Servei d’Hematologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain Vall d'Hebron Barcelona Hospital Campus Anticossos monoclonals - Ús terapèutic Hodgkin, Malaltia de - Tractament Limfomes - Tractament 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 DISEASES::Neoplasms::Neoplasms by Histologic Type::Lymphoma::Lymphoma, Non-Hodgkin::Lymphoma, T-Cell::Lymphoma, T-Cell, Peripheral DISEASES::Neoplasms::Neoplasms by Histologic Type::Lymphoma::Hodgkin Disease 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 ENFERMEDADES::neoplasias::neoplasias por tipo histológico::linfoma::linfoma no Hodgkin::linfoma de células T::linfoma de células T periféricas ENFERMEDADES::neoplasias::neoplasias por tipo histológico::linfoma::enfermedad de Hodgkin Diffuse large B-cell lymphoma; Non-Hodgkin lymphoma Limfoma difús de cèl·lules B grans; Limfoma no Hodgkin Linfoma difuso de células B grandes; Linfoma no Hodgkin Patients with relapsed or refractory lymphoma have limited treatment options, requiring newer regimens. In this Phase 1/2 study (NCT03769181), we assessed the safety, efficacy, and pharmacokinetics of isatuximab (Isa, anti-CD38 antibody) in combination with cemiplimab (Cemi, anti-programmed death-1 [PD-1] receptor antibody; Isa + Cemi) in patients with classic Hodgkin lymphoma (cHL), diffuse large B-cell lymphoma (DLBCL), and peripheral T-cell lymphoma (PTCL). In Phase 1, we characterized the safety and tolerability of Isa + Cemi with planned dose de-escalation to determine the recommended Phase 2 dose (RP2D). Six patients in each cohort were treated with a starting dose of Isa + Cemi to determine the RP2D. In Phase 2, the primary endpoints were complete response in Cohort A1 (cHL anti-PD-1/programmed death-ligand 1 [PD-L1] naïve), and objective response rate in Cohorts A2 (cHL anti-PD-1/PD-L1 progressors), B (DLBCL), and C (PTCL). An interim analysis was performed when the first 18 (Cohort A1), 12 (Cohort A2), 17 (Cohort B), and 11 (Cohort C) patients in Phase 2 had been treated and followed up for 24 weeks. Isa + Cemi demonstrated a manageable safety profile with no new safety signals. No dose-limiting toxicities were observed at the starting dose; thus, the starting dose of each drug was confirmed as the RP2D. Based on the Lugano 2014 criteria, 55.6% (Cohort A1), 33.3% (Cohort A2), 5.9% (Cohort B), and 9.1% (Cohort C) of patients achieved a complete or partial response. Pharmacokinetic analyses suggested no effect of Cemi on Isa exposure. Modest clinical efficacy was observed in patients with cHL regardless of prior anti-PD-1/PD-L1 exposure. In DLBCL or PTCL cohorts, interim efficacy analysis results did not meet prespecified criteria to continue enrollment in Phase 2 Stage 2. Isa + Cemi did not have a synergistic effect in these patient populations. This study was sponsored by Sanofi. 2023-05-12T11:26:47Z 2023-05-12T11:26:47Z 2023-02 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Carlo-Stella C, Zinzani PL, Sureda A, Araújo L, Casasnovas O, Carpio C, et al. A phase 1/2, open-label, multicenter study of isatuximab in combination with cemiplimab in patients with lymphoma. Hematol Oncol. 2023 Feb;41(1):108–19. 1099-1069 https://hdl.handle.net/11351/9525 10.1002/hon.3089 36251503 000876789000001 http://hdl.handle.net/11351/9525 eng Hematological Oncology;41(1) https://doi.org/10.1002/hon.3089 Attribution 4.0 International http://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess application/pdf Wiley Scientia