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In this Phase 1\/2 study (NCT03769181), we assessed the safety, efficacy, and pharmacokinetics of isatuximab (Isa, anti\u2010CD38 antibody) in combination with cemiplimab (Cemi, anti\u2010programmed death\u20101 [PD\u20101] receptor antibody; Isa\u00a0+\u00a0Cemi) in patients with classic Hodgkin lymphoma (cHL), diffuse large B\u2010cell lymphoma (DLBCL), and peripheral T\u2010cell lymphoma (PTCL). In Phase 1, we characterized the safety and tolerability of Isa\u00a0+\u00a0Cemi with planned dose de\u2010escalation to determine the recommended Phase 2 dose (RP2D). Six patients in each cohort were treated with a starting dose of Isa\u00a0+\u00a0Cemi to determine the RP2D. In Phase 2, the primary endpoints were complete response in Cohort A1 (cHL anti\u2010PD\u20101\/programmed death\u2010ligand 1 [PD\u2010L1] na\u00efve), and objective response rate in Cohorts A2 (cHL anti\u2010PD\u20101\/PD\u2010L1 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\u00a0weeks. Isa\u00a0+\u00a0Cemi demonstrated a manageable safety profile with no new safety signals. No dose\u2010limiting 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\u2010PD\u20101\/PD\u2010L1 exposure. In DLBCL or PTCL cohorts, interim efficacy analysis results did not meet prespecified criteria to continue enrollment in Phase 2 Stage 2. Isa\u00a0+\u00a0Cemi did not have a synergistic effect in these patient populations.<\/jats:p>","DOI":"10.1002\/hon.3089","type":"journal-article","created":{"date-parts":[[2022,10,17]],"date-time":"2022-10-17T16:38:57Z","timestamp":1666024737000},"page":"108-119","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["A phase 1\/2, open\u2010label, multicenter study of isatuximab in combination with cemiplimab in patients with lymphoma"],"prefix":"10.1002","volume":"41","author":[{"given":"Carmelo","family":"Carlo\u2010Stella","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences Humanitas University and Department of Oncology and Hematology IRCCS Humanitas Research Hospital  Milano Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2112-2651","authenticated-orcid":false,"given":"Pier 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