FDA Grants Accelerated Approval to Glofitamab-gxbm for Relapsed/Refractory Diffuse Large B-Cell Lymphoma

The FDA has approved glofitamab-gxbm (Columvi; Genentech) for adults with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) that is not otherwise specified or large B-cell lymphoma (LBCL) emerging from follicular lymphoma following 2 or more lines of systemic therapy.

The FDA granted the biologics license application (BLA) with accelerated approval based on findings from the phase 1/2 NP30179 trial regarding response rate and durability of response in the study, which were published in the New England Journal of Medicine. The FDA previously granted priority review to the BLA for glofitamab for this indication.

“People with diffuse large B-cell lymphoma who have gone through multiple lines of therapy have a poor prognosis and desperately need additional treatment options,” said Levi Garraway, MD, PhD, Genentech chief medical officer and head of Global Product Development, in a press release. “As an off-the-shelf, fixed-duration treatment providing durable response rates, we believe Columvi could change the way this aggressive lymphoma is treated, reinforcing our dedication to bringing innovative treatment options to people with critical unmet needs.”

Glofitamab targets CD3, a protein found on the surface of immune T cells, and CD20, a healthy or malignant protein that lines the surfaces of B cells. The T-cell engaging bispecific antibody activates the T cell proteins to kill cancer cells on the B cell, thus dually targeting both cells.

The investigational CD20xCD3 T-cell engaging bispecific antibody is the first therapy of its kind that is fixed-duration, off-the-shelf, and effective for patients with multiple treatments, according to Genentech.

In the NP30179 trial, glofitamab-gxbm was administered as a fixed course for 8.5 months in 132 patients with DLBCL who relapsed or were refractory to prior therapies, approximately one-third (30%) of whom were administered prior chimeric antigen receptor (CAR) T-cell therapy and 83% of whom were refractory to their most recent treatment.

The study showed that patients administered fixed-duration glofitamab-gxbm achieved durable remission. Further, 56% achieved an overall response (OR; 74/132 [95% confidence interval (CI): 47-65]) and 43% achieved a complete response (CR; 57/132 [95% CI: 35-52]).

More than two-thirds of patients who responded continued to respond for at least 9 months (68.5% [95% CI: 56.7-80.3]). The investigators also found that the median duration of response was 1.5 years (18.4 months [95% CI: 11.4-not estimable]).

The most common adverse events (AEs) associated with glofitamab-gxbm were cytokine release syndrome (CRS; 70%), musculoskeletal pain (21%), fatigue (20%) and rash (20%). The investigators reported that CRS was generally low grade, with 52% experiencing grade 1, and 14% experiencing grade 2 CRS.

Glofitamab-gxbm is administered via 13 intravenous infusions over a maximum of 12 cycles, which includes step-up dosing, or until disease progression or intolerance to therapy, whichever occurs first. Following the first cycle, glofitamab-gxbm is administered once every 3 weeks.

The treatment is designed to be completed in approximately 8.5 months, which provides patients with R/R DLBCL a target end date for the treatment course and the potential for a treatment-free period. Patients are pretreated with a single-dose of obinutuzumab 7 days before initiating therapy with glofitamab-gxbm. Patients are also administered a corticosteroid, an antipyretic, and an antihistamine as premedications to lower the risk of CRS.

Continued approval for the approved indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. Genentech said glofitamab-gxbm will be available in the United States in the weeks ahead.

“Patients with relapsed or refractory diffuse large B-cell lymphoma may experience rapid progression of their cancer and often urgently need an effective treatment option that can be administered without delay,” study investigator Krish Patel, MD, director of the Lymphoma Program at the Swedish Cancer Institute in Seattle, said in a press release. “Experience from clinical trials demonstrates that Columvi can provide patients with relapsed or refractory diffuse large B-cell lymphoma a chance for complete remission with a fixed-duration immunotherapy and that such remissions can potentially be sustained after the end of their treatment.”

Reference

FDA Approves Genentech’s Columvi, the First and Only Bispecific Antibody With a Fixed-Duration Treatment for People With Relapsed or Refractory Diffuse Large B-Cell Lymphoma. Genentech. News release. June 16, 2023. https://www.gene.com/media/press-releases/14994/2023-06-15/fda-approves-genentechs-columvi-the-firs