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Glofitamab for Relapsed or Refractory B-Cell Lymphoma


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In a phase I trial reported in the Journal of Clinical Oncology, Hutchings et al found that the bivalent CD20-targeting T-cell–engaging bispecific antibody glofitamab produced high response rates and was associated with manageable toxicity in patients with predominantly refractory aggressive B-cell non-Hodgkin lymphoma.

As related by the investigators, glofitamab has a novel 2:1 structure that permits bivalent binding to CD20 on B cells and monovalent binding to CD3 on T cells; the CD3-binding region is fused to one of the CD20-binding regions by a flexible linker that improves target effector cell binding.

Study Details

The trial included 171 patients who had received a median of three prior treatments. Overall, 74% had diffuse large B-cell lymphoma, transformed follicular lymphoma, or other aggressive histology, and the remainder had indolent lymphoma subtypes; 91% were refractory to prior therapy.

Seven days prior to administration of the first dose of glofitamab, patients received a single dose of obinutuzumab at 1,000 mg to deplete peripheral and tissue-based B cells for mitigation of serious cytokine-release syndrome. Patients then received glofitamab at 0.005 mg to 30 mg via intravenous infusion every 14 or 21 days. The clinical cutoff date was in August 2020.

KEY POINTS

  • Complete response was observed in 36.8% of all patients and in 57.1% of those receiving the recommended phase II dose.
  • Cytokine-release syndrome of any grade occurred in 50.3% of all patients and was grade 3 or 4 in 3.5%.

Toxicity

The recommended phase II dose was step-up dosing of 2.5/10/30 mg. Cytokine-release syndrome of any grade occurred in 86 patients total (50.3%, grade 3 or 4 in 3.5%), 33 (71.1%; grade 3 or 4 in 2.2%) of 46 at fixed doses of 10 mg to 25 mg, and 25 (71.4%; grade 3 or 4 in 5.8%) of 35 receiving 2.5/10/30 mg step-up dosing. Neurologic adverse events occurred in 74 (43.3%) of all patients, with immune effector cell–associated neurotoxicity syndrome (ICANS)-like events in 9 (5.3%), and in 11 (31.4%) of 35 receiving 2.5/10/30 mg step-up dosing, with ICANS-like events in 2 (5.7%).

Among adverse events considered related to glofitamab, grade ≥ 3 adverse events occurred in 31% of all patients and 42.9% of those receiving 2.5/10/30 mg step-up dosing; serious adverse events occurred in 45.0% and 51.4%. Glofitamab was discontinued due to adverse events in a total of five patients (2.9%), including two (5.7%) of those receiving 2.5/10/30 mg step-up dosing.

Responses

Activity was observed at all dose levels. Objective response and complete response rates were 53.8% and 36.8% among all patients, 63.3% and 52.0% among 98 patients receiving fixed doses of ≥ 10 mg, and 65.7% and 57.1% among those receiving 2.5/10/30 mg step-up dosing. Among all 63 patients with a complete response, 53 (84.1%) had ongoing complete response with a maximum follow-up of 27.4 months.

The investigators concluded, “In patients with predominantly refractory, aggressive B-cell non-Hodgkin lymphoma, glofitamab showed favorable activity with frequent and durable complete responses and a predictable and manageable safety profile.”

Michael J. Dickinson, MBBS, DMedSci, of Peter MacCallum Cancer Centre, Royal Melbourne Hospital, The University of Melbourne, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by F. Hoffmann-La Roche Ltd. 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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