TY - JOUR
T1 - A phase 1/2, open-label, multicenter study of isatuximab in combination with cemiplimab in patients with lymphoma
AU - Carlo-Stella, Carmelo
AU - Zinzani, Pier Luigi
AU - Sureda, Anna
AU - Araújo, Luis
AU - Casasnovas, Olivier
AU - Carpio, Cecilia
AU - Yeh, Su-Peng
AU - Bouabdallah, Krimo
AU - Cartron, Guillaume
AU - Kim, Won Seog
AU - Cordoba, Raul
AU - Koh, Youngil
AU - Re, Alessandro
AU - Alves, Daniela
AU - Chamuleau, Martine
AU - le Gouill, Steven
AU - López-Guillermo, Armando
AU - Moreira, Ilídia
AU - van der Poel, Marjolein W. M.
AU - Abbadessa, Giovanni
AU - Meng, Robin
AU - Ji, Ran
AU - Lépine, Lucie
AU - Saleem, Rao
AU - Ribrag, Vincent
N1 - Funding Information: This study was sponsored by Sanofi. The authors thank the participating patients and their families, and the study centers and investigators for their contributions to the study. Medical writing support was provided by Smitha Reddy, PhD, of Elevate Scientific Solutions, contracted by Sanofi for publication support services. Publisher Copyright: © 2022 The Authors. Hematological Oncology published by John Wiley & Sons Ltd.
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
KW - cemiplimab
KW - diffuse large B-cell lymphoma
KW - isatuximab
KW - non-Hodgkin lymphoma
KW - peripheral T-cell lymphoma
UR - http://www.scopus.com/inward/record.url?scp=85141383428&partnerID=8YFLogxK
U2 - https://doi.org/10.1002/hon.3089
DO - https://doi.org/10.1002/hon.3089
M3 - Article
C2 - 36251503
SN - 0278-0232
JO - Hematological oncology
JF - Hematological oncology
ER -