A phase 1/2, open-label, multicenter study of isatuximab in combination with cemiplimab in patients with lymphoma

C. Carlo-Stella*, P.L. Zinzani, A. Sureda, L. Araujo, O. Casasnovas, C. Carpio, S.P. Yeh, K. Bouabdallah, G. Cartron, W.S. Kim, R. Cordoba, Y. Koh, A. Re*, D. Alves, M. Chamuleau, S. Le Gouill, A. Lopez-Guillermo, I. Moreira, M.W.M. van der Poel, G. AbbadessaR. Meng, R. Ji, L. Lepine, R. Saleem, V. Ribrag

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


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] naive), 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.
Original languageEnglish
Pages (from-to)108-119
Number of pages12
JournalHematological Oncology
Issue number1
Early online date1 Oct 2022
Publication statusPublished - Feb 2023


  • cemiplimab
  • diffuse large B-cell lymphoma
  • isatuximab
  • non-Hodgkin lymphoma
  • peripheral T-cell lymphoma
  • SAR650984


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