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

J Clin Oncol. 2022 Feb 10;40(5):481-491. doi: 10.1200/JCO.21.00931. Epub 2021 Dec 16.


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 ( 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 = 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.

Publication types

  • Clinical Trial, Phase I
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Intravenous
  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Bispecific / administration & dosage*
  • Antibodies, Bispecific / adverse effects
  • Antineoplastic Agents, Immunological / administration & dosage*
  • Antineoplastic Agents, Immunological / adverse effects
  • Canada
  • Drug Administration Schedule
  • Female
  • Humans
  • Lymphoma, B-Cell / drug therapy*
  • Lymphoma, B-Cell / immunology
  • Lymphoma, B-Cell / pathology
  • Male
  • Middle Aged
  • Remission Induction
  • Time Factors
  • Treatment Outcome
  • United States
  • Young Adult


  • Antibodies, Bispecific
  • Antineoplastic Agents, Immunological

Associated data