On June 15, the U.S. Food and Drug Administration (FDA) granted accelerated approval to glofitamab-gxbm (Columvi) for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) not otherwise specified or large B-cell lymphoma arising from follicular lymphoma, after two or more lines of systemic therapy. Glofitamab is the first and only CD20 x CD3 T-cell–engaging bispecific antibody for the treatment of relapsed or refractory DLBCL that is given for a defined period of time.
While many people with DLBCL are responsive to treatment, the majority of those who relapse or are refractory to subsequent treatments have poor outcomes.
The FDA accelerated approval is based on positive results from the phase I/II NP30179 study (ClinicalTrials.gov identifier NCT03075696) of glofitamab given as a fixed course for 8.5 months in 132 patients with DLBCL who had relapsed or were refractory to prior therapies, including about one-third (30%) who had received prior chimeric antigen receptor T-cell therapy. Additionally, 83% of patients were refractory to their most recent therapy.
Results showed patients treated with fixed-duration glofitamab achieved durable remissions, with 56% of patients achieving an overall response (n = 74 of 132; 95% confidence interval [CI] = 47%–65%) and 43% of patients achieving a complete response (n = 57 of 132; 95% CI = 35%–52%). Over two-thirds—68.5%—of those who responded continued to respond for at least 9 months (95% CI = 56.7%–80.3%). The median duration of response was 18.4 months (95% CI = 11.4 months to not estimable).
Data from the NP30179 study was recently published by Dickinson et al in The New England Journal of Medicine.
Among 145 patients who received glofitamab in the study, the most common adverse events were cytokine-release syndrome (70%), musculoskeletal pain (21%), fatigue (20%), and rash (20%). Cytokine-release syndrome was generally low grade (52% of patients grade 1, and 14% grade 2).
“Patients with relapsed or refractory DLBCL may experience rapid progression of their cancer and often urgently need an effective treatment option that can be administered without delay,” said Krish Patel, MD, Director of the Lymphoma Program at the Swedish Cancer Institute in Seattle, and an investigator on the NP30179 study. “Experience from clinical trials demonstrates that glofitamab can provide patients with relapsed or refractory DLBCL a chance for complete remission with a fixed-duration immunotherapy and that such remissions can potentially be sustained after the end of their treatment.”
Unlike treat-to-progression approaches where treatment is given indefinitely until disease progression or the therapy cannot be tolerated, glofitamab is administered in 13 intravenous infusions over a maximum of 12 cycles (including step-up dosing) or until disease progression or the treatment cannot be tolerated, whichever occurs first. After cycle 1, glofitamab is administered once every 3 weeks. Designed to be completed in approximately 8.5 months, glofitamab offers patients with relapsed or refractory DLBCL a target end date for their course of treatment and the possibility of a treatment-free period. Additionally, glofitamab is a chemotherapy-free treatment option that is off-the-shelf and ready for infusion. Patients are pretreated with a single dose of obinutuzumab 7 days prior to starting glofitamab. Patients are also given a corticosteroid, an antipyretic, and an antihistamine as premedications to reduce the risk of cytokine-release syndrome.
The current indication is approved under accelerated approval based on response rate and durability of response in the phase I/II NP30179 study. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
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