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.
Lihua E Budde  1 ,  Sarit Assouline  2 ,  Laurie H Sehn  3 ,  Stephen J Schuster  4 ,  Sung-Soo Yoon  5 ,  Dok Hyun Yoon  6 ,  Matthew J Matasar  7 ,  Francesc Bosch  8 ,  Won Seog Kim  9 ,  Loretta J Nastoupil  10 ,  Ian W Flinn  11 ,  Mazyar Shadman  12 ,  Catherine Diefenbach  13 ,  Carol O'Hear  14 ,  Huang Huang  15 ,  Antonia Kwan  14 ,  Chi-Chung Li  14 ,  Emily C Piccione  14 ,  Michael C Wei  14 ,  Shen Yin  14 ,  Nancy L Bartlett  16
Affiliations
  • 1. City of Hope National Medical Center, Duarte, CA.
  • 2. Jewish General Hospital and McGill University, Montreal, Quebec, Canada.
  • 3. BC Cancer Centre for Lymphoid Cancer and The University of British Columbia, Vancouver, British Columbia, Canada.
  • 4. Lymphoma Program, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA.
  • 5. Seoul National University Hospital, Seoul, South Korea.
  • 6. Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
  • 7. Memorial Sloan Kettering Cancer Center, New York, NY.
  • 8. University Hospital Vall d'Hebron and Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain.
  • 9. Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul, South Korea.
  • 10. MD Anderson Cancer Center, Houston, TX.
  • 11. Sarah Cannon Research Institute/Tennessee Oncology, Nashville, TN.
  • 12. Fred Hutchinson Cancer Research Center, Seattle, WA.
  • 13. Perlmutter Cancer Center at NYU Langone Health, New York, NY.
  • 14. Genentech, Inc, South San Francisco, CA.
  • 15. F. Hoffmann-La Roche Limited, Mississauga, Ontario, Canada.
  • 16. Siteman Cancer Center, Washington University School of Medicine, St Louis, MO.
PMID: 34914545 DOI: 10.1200/JCO.21.00931
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 = 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.

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