FDA Approves Mosunetuzumab for Relapsed/Refractory Follicular Lymphoma

FDA

The FDA has approved mosunetuzumab-axgb (Lunsumio) for the treatment of adult patients with relapsed or refractory follicular lymphoma after 2 or more lines of systemic therapy.¹

The regulatory decision is supported by data from phase 2 GO29781 study (NCT02500407), in which the first-in-class T-cell–engaging bispecific antibody induced high and durable response rates.

Specifically, mosunetuzumab elicited an objective response rate of 80% (95% CI, 70%-88%) in the 90 patients who received it, with 57% (95% CI, 44%-70%) of patients maintaining responses for at least 18 months. The median duration of response (DOR) among responders was 22.8 months (95% CI, 10–not reached [NR]). A complete response (CR) was achieved in 60% of the patients (95% CI, 49%-70%).

“This approval is a significant milestone for people with relapsed or refractory follicular lymphoma, who have had limited treatment options until now,” Elizabeth Budde, MD, PhD, clinical trial investigator and hematologic oncologist and associate professor, City of Hope Division of Lymphoma, Department of Hematology & Hematopoietic Cell Transplantation, stated in a press release. “As a first-in-class T-cell–engaging bispecific antibody that can be initiated in an outpatient setting, Lunsumio’s high response rates and fixed-duration could change the way advanced follicular lymphoma is treated.”

The pivotal, single-arm, multicenter phase 2 expansion trial enrolled patients with follicular grade 1 to 3a who had an ECOG performance status of 0 or 1 and who had received 2 or more prior therapies, including an anti-CD20 antibody and an alkylating agent.

Study participants received mosunetuzumab intravenously in 21-day cycles with cycle 1 step-up dosing: 1 mg on cycle 1 day 1, 2 mg on cycle 1 day 8, 60 mg on cycle 1 day 15 and cycle 2 day 1, and 30 mg on day 1 of cycle 3 and onward.² Those with a CR by investigator assessment per the International Harmonisation Project criteria completed treatment after cycle 8, whereas those with a partial response or stable disease continued treatment for up to 17 cycles.

The primary end point of the trial was CR rate per independent review committee (IRC) assessment in all enrolled patients. Secondary end points included investigator-assessed CR, IRC- and investigator-assessed ORR and DOR in responders and complete responders, among others.

Previously, the trial met its primary end point when mosunetuzumab elicited an ORR of 60% compared with a historical control of 14% (P < .0001).^2,3

Updated data from the trial were presented at the 2022 ASH Annual Meeting.⁴ The median follow-up was 28.3 months (range, 2-38), and the data cutoff date was July 8, 2022 and 81% remained in follow-up.

In the 90 patients, the median age was 60 years (range, 29-90); 61% were male. Regarding performance status, 59% had a status of 0 and 41% had a status of 1. Most patients (77%) had Ann Arbor stage III/IV disease, and 23% had stage I/II disease. The median number of prior lines of therapy was 3 (range, 2-10) and 69% of patients were refractory to their last therapy. Seventy-nine percent of patients were refractory to a prior anti-CD20 therapy.

Data reported during the meeting showed that the time to first response was 1.4 months (range, 1.0-11), and the time to first CR was 3.0 months (range, 1.0-19). The median investigator-assessed progression-free survival (PFS) was 24 months (range, 12-NR); the 24-month PFS rate was 48% (95% CI, 36%-60%). The median time to next treatment was not reached (range, 18-NR). The median overall survival (OS) was NR (range, NR-NR); the 24-month OS rate was 87% (95% CI, 80%-94%).

Regarding safety, in the 218 patients with hematologic malignancies who received mosunetuzumab at the recommended dose, the most common adverse effect (AE) was cytokine release syndrome (CRS), which occurred in 39% of patients. The median duration of CRS events was 3 days (range,1-29). Other common AEs comprised fatigue, rash, pyrexia and headache.

References

1. FDA approves Genentech's Lunsumio, a first-in-class bispecific antibody, to treat people with relapsed or refractory follicular lymphoma. News release. Genentech. December 22, 2022. Accessed December 22, 2022. https://bit.ly/3hHrIUh
2. Dreyling M, Santoro A, Mollica L, et al. Phosphatidylinositol 3-kinase inhibition by copanlisib in relapsed or refractory indolent lymphoma. J Clin Oncol. 2017;35(35):3898-3905. doi:10.1200/JCO.2017.75.4648
3. Budde LE, Sehn LH, Matasar M, et al. Safety and efficacy of mosunetuzumab, a bispecific antibody, in patients with relapsed or refractory follicular lymphoma: a single-arm, multicentre, phase 2 study. Lancet Oncol. 2022;23(8):1055-1065. doi:10.1016/S1470-2045(22)00335-7
4. Bartlett NL, Sehn LH, Matasar MJ, et al. Mosunetuzumab monotherapy demonstrates durable efficacy with a manageable safety profile in patients with relapsed/refractory follicular lymphoma who received ≥2 prior therapies: updated results from a pivotal phase II study. Presented at: 2022 ASH Annual Meeting; December 10-13, 2022; New Orleans, LA. Abstract 610