FDA Grants Priority Review to Glofitamab for Relapsed/Refractory LBCL

The FDA has accepted a biologics license application (BLA) for glofitamab (RG6026; RO7082859) for the treatment of adult patients with relapsed or refractory large B-cell lymphoma (LBCL) after 2 or more lines of systemic therapy.¹

The BLA was supported by data from the pivotal phase 1/2 NP30179 trial (NCT03075696). Findings showed that at a median follow-up of 13.4 months, patients treated with the investigational CD20xCD3 T-cell engaging bispecific antibody (n = 155) experienced an objective response rate (ORR) of 51.6%, including a complete response (CR) rate of 40.0%.

Additionally, among those who achieved a CR (n = 62), 73.1% of patients continued to experience a response at 12 months, and the median duration of CR was not yet reached. The median duration of response (DOR) was 18.4 months.

“Unfortunately, people with relapsed or refractory LBCL have a poor prognosis and desperately need additional therapies that are immediately available at the time of relapse,” Levi Garraway, MD, PhD, chief medical officer and head of Global Product Development at Roche, stated 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.”

The multicenter, open-label, dose-escalation and -expansion NP30179 trial enrolled patients with relapsed/refractory diffuse LBCL who had received at least 2 lines of prior therapy. Patients were required to have measurable disease, an ECOG performance status of 0 or 1, a life expectancy of at least 12 weeks, and adequate liver, hematologic, and renal function.²

Key exclusion criteria included patients with chronic lymphocytic leukemia, Burkitt lymphoma, and lymphoplasmacytic lymphoma; a known or suspected history of hemophagocytic lymphohistiocytosis; a known active infection or reactivation of a latent infection; treatment with standard radiotherapy, any chemotherapeutic agent, or treatment with any other investigational anti-cancer agent, including CAR T-cell therapy, within 4 weeks prior to obinutuzumab (Gazyva) infusion; or prior solid organ or allogeneic stem cell transplantation.

In the study, patients received pretreatment with obinutuzumab to mitigate cytokine release syndrome (CRS), followed by fixed-duration glofitamab monotherapy for 12 cycles. Glofitamab was administered at step-up doses of 2.5 mg on day 8 and 10 mg on day 15 of cycle 1, followed by 30 mg on day 1 of cycles 2 through 12.

The primary end point of the trial was CR rate per independent review committee. Secondary end points consisted of ORR, DOR, progression-free survival (PFS), safety, and tolerability.

Previously reported data presented at the 2022 ASH Annual Meeting and published in The New England Journal of Medicine in December 2022 showed that at a median follow-up of 12.6 months, the CR rate was 39% (95% CI, 32%-48%), and the median time to CR was 42 days (95% CI, 42-44).³ Additionally, 78% of complete responders had an ongoing response at 12 months. The 12-month PFS rate was 37% (95% CI, 28%-46%).

Regarding safety, the most common adverse effect was CRS. Grade 1 CRS occurred in 48.1% of patients, and 12.3% of patients had grade 2 CRS. Most CRS events were associated with initial administration of glofitamab during cycle 1. Grade 3 or higher CRS occurred in 3.9% of patients, and no grade 5 events were reported. One patient discontinued glofitamab due to CRS.

References

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 5, 2023. Accessed January 6, 2023. https://bit.ly/3GNH0AB
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://www.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. 2022;387(24):2220-2231. doi:10.1056/NEJMoa2206913