Glofitamab Approaches EU Approval for R/R Diffuse Large B-cell Lymphoma

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended the approval of glofitamab (Columvi) for fixed-duration use in adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) following 2 or more lines of systemic therapy.¹

The recommendation is supported by findings from a key cohort in the phase 1/2 NP30179 study (NCT03075696); notably, 83.3% of these patients were refractory to their most recent therapy and 90% were refractory to any prior line of treatment. Additionally, 35.2% of these patients previously received CAR T-cell therapy.

When the agent was administered at a fixed course, it elicited a complete response (CR) rate of 35.2% (n = 38/108) and an overall response rate (ORR) of 50% (n = 54). The majority (74.6%; 95% CI, 59.19%-89.93%) of those who achieved a CR with glofitamab continued to respond at 1 year. The median follow-up for duration of response (DOR) was 12.8 months in this group, but the median duration of CR had not yet been reached. The median time to first CR with the agent was 42 days (95% CI, 41-47).

The most common toxicity observed with glofitamab was cytokine release syndrome (CRS; 64.3%); this was grade 1 in 48.1% of patients and grade 2 in 12.3% of patients. Only 1 patient discontinued treatment due to CRS. Other common adverse effects (AEs) experienced with the agent included neutropenia (37.7%), anemia (30.5%), and thrombocytopenia (24.7%).

“New therapeutic options that are readily and broadly available are urgently needed for people with relapsing DLBCL, which can become fatal without immediate treatment,” Levi Garraway, MD, PhD, chief medical officer and head of Global Product Development at Roche, stated in a news release. “The CHMP’s recommendation for [glofitamab] brings us closer to providing a new, fixed-duration therapy for people with DLBCL that induces early and long-lasting responses.”

Data from a larger cohort of the multicenter, open-label, phase 1/2 study that were published in the New England Journal of Medicine emphasize the durable activity achieved with glofitamab.²

The study included patients with histologically confirmed DLBCL, transformed follicular lymphoma, high-grade B-cell lymphoma, or primary mediastinal large B-cell lymphoma (PMBCL) who were at least 18 years of age and had an ECOG performance status of 0 or 1. To be eligible, all patients must have disease that relapsed following, or that was refractory to, at least 2 previous lines of treatment that included at least 1 CD20 antibody–based regimen and at least 1 anthracycline-containing regimen.

Patients were pretreated with obinutuzumab (Gazyva), given at a dose of 1000 mg 1 week prior to their first dose of glofitamab. Subsequently, glofitamab was given as step-up doses of 2.5 mg on day 8 and 10 mg of day 15 of the first cycle, and then at 30 mg on day 1 of cycles 2 to 12. Treatment was continued for 12 cycles or until progressive disease or intolerable toxicity.

The primary end point of the trial was CR by independent review committee (IRC) assessment. Secondary end points comprised ORR, DOR, duration of CR, time to first CR, and time to first objective response—all of which were evaluated by IRC and study investigators. Other end points included investigator-assessed CR, progression-free survival, and overall survival.

In 155 patients with heavily pretreated or refractory DLBCL, glofitamab elicited a CR rate of 39.4% (n = 61; 95% CI, 32%-48%) by IRC, with a median DOR of 18.4 months (95% CI, 13.7-not reached). The median time to first CR was 42 days (95% CI, 42-44), with most responses observed at the time of the first response assessment which was done at about 1.4 months following treatment initiation. Moreover, the ORR was 51.6% (95% CI, 43%-60%) with glofitamab.

Again, the most common toxicity reported with the agent was CRS; this effect was grade 1 in 47.4% of patients and grade 2 in 11.7% of patients. The toxicity was observed at initial doses of glofitamab.

For 3.2% of patients, glofitamab-related AEs resulted in treatment discontinuation.

In January 2023, the FDA granted priority review to a biologics license application seeking the approval of glofitamab for adult patients with relapsed or refractory large B-cell lymphoma following 2 or more lines of systemic treatment.³ The application was supported by findings from NP30179, and the agency is expected to decide by July 1, 2023.

Two months later, in March 2023, Health Canada authorized the use of glofitamab in adult patients with relapsed or refractory DLBCL not otherwise specified (NOS), DLBCL arising from follicular lymphoma, or PMBCL who previously received 2 or more lines of systemic treatment and who were not able or eligible to receive CAR T-cell therapy or who have received prior CAR T.⁴ The decision was also based on data from NP30179.

If approved, fixed-duration glofitamab will be the first CD20 x CD3 T cell–engaging bispecific antibody available to treat European patients with DLBCL following several lines of therapy, according to Roche.¹

References

1. CHMP recommends EU approval of Roche’s fixed-duration Columvi (glofitamab) for people with relapsed or refractory diffuse large B-cell lymphoma. News release. Roche. April 26, 2023. Accessed April 26, 2023. https://www.roche.com/media/releases/med-cor-2023-04-26b
2. 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
3. FDA grants priority review to Roche’s bispecific antibody glofitamab for people with relapsed or refractory large B-cell lymphoma. News release. Genentech. January 5, 2023. Accessed April 26, 2023. https://www.gene.com/media/press-releases/14980/2023-01-05/fda-grants-priority-review-to-genentechs
4. Columvi (glofitamab for injection) receives Health Canada authorization for adult patients with relapsed or refractory diffuse large B-cell lymphoma. News release. Roche. March 25, 2023. Accessed April 26, 2023.