A phase 1/2, open-label, multicenter study of isatuximab in combination with cemiplimab in patients with lymphoma.
cemiplimab
diffuse large B-cell lymphoma
isatuximab
non-Hodgkin lymphoma
peripheral T-cell lymphoma
Journal
Hematological oncology
ISSN: 1099-1069
Titre abrégé: Hematol Oncol
Pays: England
ID NLM: 8307268
Informations de publication
Date de publication:
Feb 2023
Feb 2023
Historique:
revised:
30
09
2022
received:
11
06
2022
accepted:
11
10
2022
pubmed:
18
10
2022
medline:
3
2
2023
entrez:
17
10
2022
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 36251503
doi: 10.1002/hon.3089
pmc: PMC10092787
doi:
Substances chimiques
isatuximab
R30772KCU0
cemiplimab
6QVL057INT
B7-H1 Antigen
0
Antibodies, Monoclonal, Humanized
0
Types de publication
Multicenter Study
Clinical Trial, Phase II
Clinical Trial, Phase I
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
108-119Subventions
Organisme : Sanofi
Informations de copyright
© 2022 The Authors. Hematological Oncology published by John Wiley & Sons Ltd.
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