FDA Grants Priority Review to Mosunetuzumab for Relapsed/Refractory Follicular Lymphoma

The FDA has accepted a biologics license application (BLA) and granted a priority review designation to mosunetuzumab (Lunsumio), a potential first-in-class CD20 and CD3 T-cell engaging bispecific antibody, for the treatment of patients with relapsed/refractory follicular lymphoma (FL) following at least 2 prior systemic therapies.¹

The BLA is based on findings from the pivotal phase 1/2 GO29781 trial (NCT02500407). Data from the study showed that mosunetuzumab led to high complete response (CR) rates, with most responders (57%; 95% CI, 49%-70%) maintaining responses for at least 18 months. Furthermore, the agent produced manageable tolerability in patients with heavily pretreated FL.

Roche, the manufacturer of mosunetuzumab, expects the agency to decide on the approval by December 29, 2022.

“New therapeutic options are needed for follicular lymphoma, which often relapses after initial therapy and becomes increasingly difficult to treat each time it returns. Clinical trial results have demonstrated durable responses with Lunsumio in advanced follicular lymphoma, representing a step toward shifting the treatment paradigm,” Levi Garraway, MD, PhD, chief medical officer and head of Global Product Development at Roche, stated in a press release. “Since Lunsumio does not require the collection or genetic modification of patient cells, it could become an effective, fixed-duration outpatient option without the barriers of travelling to a major academic centre.”

Previously, the FDA granted a breakthrough therapy designation to mosunetuzumab for the treatment of patients with relapsed/refractory FL who have received at least 2 prior systemic therapies in June 2020. The agency granted mosunetuzumab an orphan drug designation in December 2018.

In June 2022, the European Commission granted conditional marketing authorization for mosunetuzumab for the treatment of patients with relapsed/refractory follicular lymphoma who have received at least 2 prior systemic therapies. The commission also based that decision on results GO29781.²

GO29791 is a multicenter, open-label, dose-escalation and -expansion study evaluating the safety, efficacy, and pharmacokinetics of mosunetuzumab in patients with relapsed/refractory B-cell non-Hodgkin lymphoma. To be eligible for enrollment, patients had to have grade 1 to 3a disease, an ECOG performance status of 0 to 1, and at least 2 prior treatments consisting of at least 1 anti-CD20 antibody and at least 1 alkylating agent.

The primary end point is the CR rate per independent review facility, with key secondary end points of objective response rate (ORR), duration of response (DOR), progression-free survival, safety, and tolerability.

Additional findings presented for the first time at the 2021 American Society of Hematology Annual Meeting & Exposition showed that after a median follow-up of 18.3 months, mosunetuzumab induced a CR rate of 60% (n = 54/90) and an ORR of 80% (n = 72/90). The median DOR among responders was 22.8 months (95% CI, 9.7-not estimable).

In terms of safety, the most common adverse effect (AE) was cytokine release syndrome (39%; n = 86/218), which was generally low grade (grade 1, 25.6%; grade 2, 14.0%; grade 3, 2.3%; grade 4, 0.5%). All events resolved by the end of treatment.

Other common AEs occurring in more than 20% of patients included fatigue, headache, neutropenia, fever, and hypophosphatasemia. Treatment was administered without mandatory hospitalization.

Mosunetuzumab is currently also under study in the phase 3 CELESTIMO (NCT04712097) and SUNMO (NCT05171647) trials, which are evaluating the agent as second- and later-line therapy in combination with lenalidomide (Revlimid) in follicular lymphoma and in combination with polatuzumab vedotin-piiq (Polivy) in diffuse large B-cell lymphoma.

References

1. FDA grants priority review to Roche’s Lunsumio for people with relapsed or refractory follicular lymphoma. News release. Roche. July 6, 2022. Accessed July 6, 2022. https://bit.ly/3NLTZ5Z
2. European Commission approves Roche’s first-in-class bispecific antibody Lunsumio for people with relapsed or refractory follicular lymphoma. News release. Roche. June 8, 2022. Accessed July 6, 2022. https://bit.ly/3H7bwDT