FDA Accepts BLA and Grants Priority Review for Glofitamab in R/R LBCL


Based on data from a phase 1/2 study, a biologics license application has been accepted for glofitimab and the product has been granted priority review to for relapsed/refractory large B-cell lymphoma.

The FDA has accepted a biologics license application (BLA) and granted priority review for glofitamab (RG6026), an investigational CD20xCD3 T-cell engaging bispecific antibody, for the treatment of adult patients with relapsed or refractory (R/R) large B-cell lymphoma (LBCL) after 2 or more lines of systemic therapy.1

The basis of the BLA and priority review come from findings from the pivotal phase 1/2 NP30179 study (NCT03075696) in which glofitamab led to durable response rates in patients with heavily pre-treated LBCL. Patients enrolled achieved a 40% complete response (CR).

“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 of Roche, in the 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.”

In the phase 1/2 multicenter, open-label, dose-escalation, and dose-expansion NP30179 study, investigators aim to determine the safety, efficacy, and pharmacokinetics of glofitamab in patients with R/R LBCL.2

Patients included in the trial are those 18 years and older and must have previously received multiple courses of therapy. Patients must have measurable disease, an ECOG performance status of 0-1, a life expectancy of 12 weeks or greater, adequate liver, hematological, and renal function, resolved to grade 1 or less adverse events from prior anti-cancer therapy, and provide a fresh biopsy.

Among those enrolled, 85.1% of patients were refractory to their most recent therapy and 33.1% of patients had received prior chimeric antigen receptor T-cell therapy.

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.

Findings showed that among the 155 included in the trial, 40.0% (n = 62) achieved a CR and 51.6% (n = 80) achieved an objective response. The median follow-up time was 13.4 months. Additionally, of patients who achieved a CR, 73.1% continued to experience a response at 12 months. The median duration of CR was not reached but the median duration of response was 18.4 months.

Earlier cut-off of data from the study were presented at the American Society of Hematology 2022 Annual Meeting and published in the New England Journal of Medicine in December 2022. Data revealed that when glofitamab was administered as a fixed-duration treatment, patients had early and durable CRs and most patients who had achieved a CR at the end of treatment experienced durable responses.3

From the end of treatment, the median CR follow-up was 11.5 months (95% CI], 10.5-16.4). Sixty-one patients had also maintained a CR 12 months after the end of treatment with glofitamab and 92.6% of patients remained progression-free. Only 1 patient among 44 experienced disease progression.

Regarding safety, the most common AE was cytokine release syndrome (CRS), however, it was generally low grade with 48.1% of patients having grade 1 CRS and 12.3% having grade 2. Most of these CRS events were linked with initial administration of glofitamab. Additionally, only the incidence of grade 3 or higher CRS was 3.9%, no grade 5 events were seen, and only 1 patient of the 155 enrolled discontinued glofitamab due to CRS.

It is expected that the FDA will decide on the approval of glofitimab by July 2023. If approved, the product would be the first fixed-duration CD20/CD3 T-cell engaging bispecific antibody approved to treat this aggressive type of non-Hodgkin lymphoma.

  1. FDA grants priority review to Roche’s bispecific antibody glofitamab for people with relapsed or refractory large B-cell lymphoma. News release. Roche. January 6, 2023. Accessed January 6, 2023.
  2. A dose escalation study of glofitamab (RO7082859) as a single agent and in combination with obinutuzumab, administered after a fixed, single pre-treatment dose of obinutuzumab in participants with relapsed/refractory B-cell non-hodgkin's lymphoma. ClinicalTrials.gov. Updated December 23, 2022. Accessed January 6, 2023. https://clinicaltrials.gov/ct2/show/NCT03075696
  3. Dickinson MJ, Carlo-Stella C, Morschhauser F, et al. Glofitamab for relapsed or refractory diffuse large B-cell lymphoma. N Engl J Med. Published online December 11, 2022. doi:10.1056/NEJMoa2206913
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