FDA Approves Glofitamab for Relapsed/Refractory DLBCL

• The FDA has approved glofitamab-gxbm (Columvi) under the accelerated approval program as a result of the response rate and durability of response shown with the drug.
• The approval was supported by results from the phase 1/2 NP30179 study (NCT03075696).
• Continued approval for this indication may be contingent upon proof of the agent’s clinical benefit in a confirmatory trial.

The FDA granted accelerated approval to glofitamab-gxbm for 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

In the phase 1/2 NP30179 trial, glofitamab generated a 56% overall response rate (ORR) and 43% complete response (CR) with 68.5% of patients who achieved a response continuing to respond for at least 9 months (95% CI, 56.7-80.3). Moreover, the median duration of response was 18.4 months (95% CI, 11.4-not estimable).

“We've been waiting for such products where it would help these patients. It's also a benefit that is off the shelf, so you don't have to wait for manufacturing and the time it takes for the T-cell collection which makes it sometimes difficult for patients to get to chimeric antigen receptor [CAR] T. I think this is going to bridge a lot of those problems and fill up a needed space for patients,” Cyrus M. Khan, MD, hematologist in the Division of Hematology and Cellular Therapy at West Penn Hospital of Allegheny Health Network, told Targeted Oncology^TM.

Glofitimab is the first and only CD20xCD3 T-cell engaging bispecific antibody for the treatment of relapsed/refractory DLBCL. Treatment with glofitamab is administered for a fixed period of time or until disease progression or the treatment cannot be tolerated, whichever occurs first. After cycle 1, glofitamab is given once every 3 weeks.

“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,” said Krish Patel, MD, director of the Lymphoma Program at the Swedish Cancer Institute, and study investigator in a press release. “Experience from clinical trials demonstrates that [glofitimab] 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.”

The multicenter, open-label, dose-escalation, and dose-expansion NP30179 trial administered glofitamab to 132 patients with relapsed/refractory DLBCL as a fixed course for 8.5 months. A total of 30% of patients had received prior chimeric antigen receptor T-cell therapy and 83% were refractory to their most recent treatment.

The primary end point of the trial is CR rate by an independent review committee and secondary end points include overall response rate, duration of response, progression-free survival, safety, and tolerability.

For safety, the most common adverse events (AEs) seen in 145 included cytokine release syndrome (CRS; 70%), musculoskeletal pain (21%), fatigue (20%) and rash (20%). However, CRS was generally low grade at grade 1 (52%) and grade 2 (14%).

“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, chief medical officer and head of Global Product Development, Genentech, the developer of glofitamab, 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.”

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 16, 2023. https://tinyurl.com/3hwsvvrb

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