A phase 1/2, open-label, multicenter study of isatuximab in combination with cemiplimab in patients with lymphoma
Carlo-Stella, Carmelo (Humanitas Research Hospital (Itàlia))
Zinzani, Pier Luigi (IRCCS Azienda Ospedaliero-Universitaria di Bologna)
Sureda, Anna (Hospital Universitari de Bellvitge)
Araújo, Luis (Universitário de Coimbra)
Casasnovas, Olivier (CHU Dijon Bourgogne)
Carpio Segura, Cecilia del Carmen (Hospital Universitari Vall d'Hebron)
Yeh, Su-Peng (China Medical University Hospital)
Bouabdallah, Krimo (Bordeaux University Hospital (França))
Cartron, Guillaume (Centre Hospitalier Universitaire Montpellier)
Kim, Won Seog (Samsung Medical Center)
Cordoba, Raul (Hospital Universitario Fundación Jiménez Díaz)
Koh, Youngil (Seoul National University Hospital)
Re, Alessandro (Azienda Ospedaliera Spedali Civili di Brescia (Brescia, Itàlia))
Alves, Daniela (Centro Hospitalar Universitário Lisboa Norte)
Chamuleau, Martine (Vrije Universiteit Amsterdam)
Le Gouill, Steven (Institut Curie)
López Guillermo, Armando (Hospital Clínic i Provincial de Barcelona)
Moreira, Ilídia (Portuguese Institute of Oncology of Porto)
van der Poel, Marjolein W. M. (Maastricht University Medical Center)
Abbadessa, Giovanni (Sanofi)
Meng, Robin (Sanofi)
Ji, Ran (Sanofi)
Lépine, Lucie (Sanofi)
Saleem, Rao (Sanofi)
Ribrag, Vincent (Institut Gustave Roussy (Villejuif, França))
Universitat Autònoma de Barcelona

Fecha:	2022
Resumen:	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.
Derechos:	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.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Cemiplimab ; Diffuse large B-cell lymphoma ; Isatuximab ; Non-hodgkin lymphoma ; Peripheral T-cell lymphoma
Publicado en:	Hematological Oncology, Vol. 41 (october 2022) , p. 108-119, ISSN 1099-1069

DOI: 10.1002/hon.3089
PMID: 36251503

12 p, 600.5 KB

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