Single-Agent Mosunetuzumab Shows Durable Complete Responses in Patients with Relapsed or Refractory B-Cell Lymphomas: Phase I Dose-Escalation Study

Lihua E. Budde, Sarit Assouline, Laurie H. Sehn, Stephen J. Schuster, Sung Soo Yoon, Dok Hyun Yoon, Matthew J. Matasar, Francesc Bosch, Won Seog Kim, Loretta J. Nastoupil, Ian W. Flinn, Mazyar Shadman, Catherine Diefenbach, Carol O'Hear, Huang Huang, Antonia Kwan, Chi Chung Li, Emily C. Piccione, Michael C. Wei, Shen YinNancy L. Bartlett

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

PURPOSE Mosunetuzumab is a bispecific antibody targeting CD20 and CD3 that redirects T cells to engage and eliminate malignant B cells and is being developed for relapsed or refractory (R/R) B-cell non-Hodgkin lymphomas (B-NHLs). METHODS This first-in-human trial (ClinicalTrials.gov identifier: NCT02500407) evaluated the safety and tolerability and efficacy of mosunetuzumab in patients with R/R B-NHL and established the recommended phase II dose. Data from dose escalation are presented. Single-agent mosunetuzumab was administered intravenously in 3-week cycles, at full dose in cycle 1 day 1 (group A) or with ascending (step-up) doses during cycle 1 on days 1, 8, and 15 (group B), for eight or 17 cycles on the basis of tumor response. RESULTS Two hundred thirty patients were enrolled. Doses up to 2.8 mg and 60 mg were assessed in groups A and B, respectively; maximum tolerated dose was not exceeded. In group B (n 5 197), common adverse events ($ 20% of patients) were neutropenia (28.4%), cytokine release syndrome (27.4%), hypophosphatemia (23.4%), fatigue (22.8%), and diarrhea (21.8%). Cytokine release syndrome was mostly low-grade (grade $ 3: 1.0%) and mainly confined to cycle 1. Across the doses investigated (group B), best overall response rates were 34.9% and 66.2% in patients with aggressive and indolent B-NHL, respectively, and complete response rates were 19.4% and 48.5%. Among patients with a complete response, the median duration of response was 22.8 months (95% CI, 7.6 to not estimable) and 20.4 (95% CI, 16 to not estimable) in patients with aggressive and indolent B-NHL, respectively. CONCLUSION Mosunetuzumab, administered with step-up dosing, has a manageable safety profile and induces durable complete responses in R/R B-NHL. The expansion stage of the study is ongoing at the dose level of 1/2/60/60/30 mg selected for further study.

Original languageEnglish
Pages (from-to)481-491
Number of pages11
JournalJournal of Clinical Oncology
Volume40
Issue number5
DOIs
StatePublished - Feb 10 2022

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