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Bispecific Antibody Mosunetuzumab in Relapsed or Refractory B-Cell Lymphomas


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In a phase I study reported in the Journal of Clinical Oncology, L. Elizabeth Budde, MD, PhD, and colleagues found that the CD20-CD3 bispecific antibody mosunetuzumab produced durable responses in patients with relapsed or refractory aggressive and indolent B-cell non-Hodgkin lymphomas. 

Mosunetuzumab targets CD20 (B cells) and CD3 (T cells), redirecting T cells to engage and eliminate malignant B cells.

L. Elizabeth Budde, MD, PhD

L. Elizabeth Budde, MD, PhD

Study Details

The first-in-human international trial enrolled patients into two groups receiving intravenous mosunetuzumab in 3-week cycles: 33 patients in group A received fixed doses of up to 2.8 mg on day 1; 197 patients in group B received ascending doses during cycle 1 on days 1, 8, and 15, with treatment continuing for 8 or 17 cycles based on tumor response. Maximum tolerated dose was not reached in either group. In group B, dose escalation at 1/2/13.5 mg was evaluated in 43 patients with follicular lymphoma. Thereafter, dosing was modified to 1/2/60 mg in cycle 1, 60 mg on day 1 of cycle 2, and 30 mg on day 1 of subsequent cycles (1/2/60/60/30-mg dosing scheme).

The data presented are from group B. The clinical cutoff date was in January 2020.

Responses  

Across the doses investigated, best overall response rates were 34.9% among 129 patients with aggressive disease and 66.2% among 68 with indolent disease, with complete response rates of 19.4% and 48.5%, respectively.

Among patients with aggressive disease, median response durations were 7.6 months (95% confidence interval [CI] = 5.6–22.8 months) among all responders and 22.8 months (95% CI = 7.6 months–not estimable) among those with complete response. Among patients with indolent disease, median response durations were 16.8 months (95% CI = 11.7 months–not estimable) and 20.4 months (95% CI = 16.0 months–not estimable), respectively. Median time to first response was 1.4 months (range = 1.1–13.8 months) and 2.6 months (range = 1.2–7.5 months) in responders with aggressive and indolent disease, respectively.

Median progression-free survival was 1.4 months (95% CI = 1.4–2.9 months) among patients with aggressive disease and 11.8 months (95% CI = 8.4 months–not estimable) among those with indolent disease.

KEY POINTS

  • Across the doses investigated, best overall response rates were 34.9% among 129 patients with aggressive disease and 66.2% among 68 with indolent disease, with complete response rates of 19.4% and 48.5%, respectively.
  • Grade ≥ 3 adverse events occurred in 71.1% of patients.
  • The expansion stage of the study is ongoing at the dose level of 1/2/60/60/30 mg selected for further study.

Adverse Events

Most adverse events (53.7%) occurred during the first 21 days of treatment. The most common adverse events of any grade were neutropenia (28.4%), cytokine-release syndrome (27.4%; grade 3 in 1.0%), hypophosphatemia (23.4%), fatigue (22.8%), and diarrhea (21.8%). Grade ≥ 3 adverse events occurred in 71.1% of patients, most commonly neutropenia (25.4%), hypophosphatemia (15.2%), and anemia (9.1%). Treatment-related adverse events led to treatment discontinuation in seven patients (3.6%). Treatment-related death occurred in two patients, due to hemophagocytic lymphohistiocytosis and pneumonia, respectively.

The investigators concluded, “Mosunetuzumab, administered with step-up dosing, has a manageable safety profile and induces durable complete responses in relapsed or refractory B-cell non-Hodgkin lymphomas. The expansion stage of the study is ongoing at the dose level of 1/2/60/60/30 mg selected for further study.”

Nancy L. Bartlett, MD, of Washington University School of Medicine in St. Louis, Siteman Cancer Center, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by Genentech, Inc. For full disclosures of the study authors, visit ascopubs.org.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
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