FDA Approves Glofitamab-gxbm for Relapsed/Refractory DLBCL

FDA

The FDA has granted accelerated approval to glofitamab-gxbm (Columvi) for the treatment of adult patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) not otherwise specified or large B-cell lymphoma arising from follicular lymphoma, after at least 2 lines of systemic therapy.¹

The approval was based on findings from the phase 1/2 NP30179 trial (NCT03075696),² in which glofitamab, a CD20xCD3 T-cell engaging bispecific antibody, demonstrated a 56% overall response rate (ORR) and a complete response (CR) rate of 43%. Moreover, 68.5% of patients who achieved a response continued to respond for 9 months or longer (95% CI, 56.7-80.3). The median duration of response was 18.4 months (95% CI, 11.4-not estimable).

“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, stated in a news 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.”

Seven days prior to glofitamab therapy, patients are pretreated with a single dose of obinutuzumab (Gazyva). Patients also received a corticosteroid, antipyretic, and an antihistamine as pretreatment to reduce the risk of cytokine release syndrome (CRS).

Glofitamab is then administered in 13 intravenous infusions over up to 12 cycles, which includes step-up dosing, or until disease progression or intolerance, whichever occurs first. Following cycle 1 of treament, glofitamab is given once every 3 weeks.

Genentech, the developer of glofitamab, noted in the news release that glofitamab will be available in the United States in the coming weeks.

In the multicenter, open-label, dose-escalation, and dose-expansion trial, glofitamab was administered as a fixed course for 8.5 months in 132 patients with DLBCL who were relapsed or refractory to prior treatment; 30% of patients had received prior CAR T-cell therapy and 83% were refractory to their most recent treatment.

Regarding safety, the most common adverse events (AEs; n = 145) were CRS (70%), musculoskeletal pain (21%), fatigue (20%) and rash (20%). CRS was found to be mostly low grade at grade 1 (52%) and grade 2 (14%).

The continued approval for glofitamab's indication may be contingent upon the results of a confirmatory trial.

“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,” Levi Garraway, MD, PhD, chief medical officer and head of Global Product Development, Genentech, the developer of glofitamab, said in a news 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.”

WATCH: Carmelo Carlo-Stella, MD, PhD, of IRCCS Humanitas Research Hospital, discusses the FDA approval of glofitamab-gxbm for the treatment of patients with relapsed/refractory DLBCL not otherwise specified or large B-cell lymphoma arising from follicular lymphoma, after at least 2 lines of systemic therapy.

References

1. 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. News release. Genentech. June 15, 2023. Accessed June 15, 2023. https://www.gene.com/media/press-releases/14994/2023-06-15/fda-approves-genentechs-columvi-the-firs
2. Dickinson MJ, Carlo-Stella C, Morschauser F, et al. Glofitamab for relapsed or refractory diffuse large B-cell lymphoma. N Eng J Med. 2022;387(24):2220-2231. doi:10.1056/NEJMoa2206913