FDA Grants Priority Review to Glofitamab for Relapsed/Refractory Large B-Cell Lymphoma

The FDA has granted priority review to a biologics license application (BLA) for glofitamab (Genentech) for adult patients with relapsed or refractory (R/R) large B-cell lymphoma (LBCL) who have had 2 or more lines of systemic therapy.

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

“Unfortunately, people with relapsed or refractory large B-cell lymphoma have a poor prognosis and desperately need additional therapies that are immediately available at the time of relapse,” said Levi Garraway, MD, PhD, chief medical officer and head of Global Product Development, in a press release. “Even for patients whose cancer is rapidly progressing, glofitamab given for a fixed duration has shown impressive efficacy and long-term durability, with patients continuing to experience a complete remission after treatment has concluded.”

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.

Following glofitamab treatment, 40% of participants in the NP30179 study showed a complete response (CR) with no visible signs of cancer, and 51.6% of patients showed an objective response (OR) of less cancer present in the body.

LBCL is among the most prevalent blood cancers in the United States. The aggressive, fast-growing, form of non-Hodgkin lymphoma (NHL) accounts for approximately 33% of NHL diagnoses. Among patients with NHL, 4 out of every 10 do not respond to standard treatment, and subsequent therapies are not usually as effective, which leads to poor outcomes.

The phase 1/2, multicenter, open-label, dose-escalation and expansion NP30179 study assessed the safety, efficacy, and pharmacokinetics of glofitamab in patients with R/R LBCL. The primary endpoint measured CR, with secondary endpoints that measured outcomes of OR, duration of response, progression-free survival (PFS), safety, and tolerability.

At 12 months, 73.1% of patients experienced CR, with 92.6% of of patients remaining progression-free. The median duration of response was 18.4 months, considered a durable response.

Cytokine release syndrome was the most reported adverse event (AE). It was low-grade 1 and 2 for most patients, and there were no grade 5 AEs reported.

These findings were presented at the 64th American Society of Hematology 2022 Annual Meeting and were published in the New England Journal of Medicine in December 2022.

Reference

Genentech. FDA Grants Priority Review to Genentech’s Bispecific Antibody Glofitamab for People With Relapsed or Refractory Large B-Cell Lymphoma. News Release. January 5, 2023. Accessed on January 6, 2023. https://www.gene.com/media/press-releases/14980/2023-01-05/fda-grants-priority-review-to-genentechs