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The European Medicines Agency’s Committee for Medicinal Products for Human Use has recommended approval under conditional marketing authorization for mosunetuzumab for use in adult patients with relapsed or refractory follicular lymphoma who have previously received at least 2 therapies.
The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended approval under conditional marketing authorization for mosunetuzumab for use in adult patients with relapsed or refractory follicular lymphoma who have previously received at least 2 therapies.1
The recommendation from the committee is based on positive findings from the phase 1/2 GO29781 trial (NCT02500407). At a median follow-up of 18.3 months, the first-in-class CD20 x CD3 T-cell–engaging bispecific antibody elicited an objective response rate of 80% (95% CI, 70%-88%) in patients with heavily pretreated follicular lymphoma (n = 72/90), with a complete response (CR) rate of 60% (95% CI, 49%-70%) per independent review facility (IRF) assessment.
Moreover, the median duration of response (DOR) with mosunetuzumab was 22.8 months (95% CI, 9.7–not evaluable [NE]). The median progression-free survival with the agent was 17.9 months (95% CI, 10.1-NE).
“The majority of people with follicular lymphoma experience frequent relapses, and with each successive therapy, the duration of remission and survival shortens,” Levi Garraway, MD, PhD, chief medical officer and head of Global Product Development at Roche, stated in a press release. “Today’s decision acknowledges the potential of mosunetuzumab as an efficacious, readily available, fixed-duration option, and brings the possibility of new hope to people living with this disease.”
In the phase 1 experience (NCT02500407), mosunetuzumab was delivered intravenously (IV) with step-up dosing in cycle 1 to mitigate toxicities such as cytokine release syndrome (CRS) and was found to produce encouraging activity with a tolerable safety profile in those with relapsed or refractory follicular lymphoma who received 2 or more prior therapies.
The single-arm, phase 2, expansion portion of the trial enrolled those with follicular lymphoma who had grade 1 to 3a disease and an ECOG performance status of 0 or 1. To be eligible for enrollment. Patients needed to have received 2 or more prior regimens, including at least 1 anti-CD20 antibody and at least 1 alkylating agent.
Ninety participants were given IV mosunetuzumab every 3 weeks in 21-day treatment cycles using a step-up dosing approach in the first cycle. Here, the agent was administered at 1 mg on day 1, at 2 mg on day 8, and at 60 mg on day 15. In the second cycle, mosunetuzumab was given at a dose of 60 mg on day 1. For cycle 3 and beyond, the agent was given at a dose of 30 mg on day 1. If a CR was achieved after cycle 8 of treatment, patients were given 17 cycles of treatment. Hospitalization was not mandatory for patients.
The primary end point of the research was CR rate per IRF assessment, and this was examined in comparison with the historical CR rate of 14%. Secondary end points included ORR, DOR, and PFS, as well as safety and tolerability.
The majority of patients had advanced disease, were heavily pretreated, and had poor-prognosis characteristics.
The median age of study participants was 60 years (range, 29-90, and more than half of patients (61.1%) were male. Regarding performance status, 58.9% of patients had a status of 0 and 41.1% had a status of 1. Moreover, 23.3% of patients had Ann Arbor stage I to II disease, and 76.7% had stage III to IV disease.
The median number of prior lines of treatment received was 3 (range, 2-10), with all patients having received an anti-CD20 therapy and an alkylator therapy. Moreover, 18.9% of patients received prior PI3K inhibitors, 14.4% received immunomodulatory drugs, and 3.3% received CAR T-cell therapy.
Approximately 21% (21.1%) of patients previously received autologous stem cell transplant. Most patients (68.9%) were refractory to their last therapy received. Moreover, 78.9% were refractory to a prior anti-CD20 therapy and 53.3% were double refractory to an anti-CD20 therapy and an alkylator therapy. Notably, 52.2% of patients had POD24 disease.
Additional data presented during the 2021 ASH Annual Meeting showed that the investigator-assessed CR rate achieved with mosunetuzumab was also 60% (95% CI, 49%-70%). The investigator-assessed ORR with the agent was 78% (95% CI, 68%-86%).
Moreover, the CR rate achieved with mosunetuzumab in high-risk subsets were comparable with the overall population. Specifically, the CR rate in those younger than 65 years (n = 60) was 55% (95% CI, 42%-68%) and the CR rate was 70% (95% CI, 51%-85%) in those aged 65 years and older (n = 30). In those who previously received 2 lines of therapy (n = 34), the CR rate was 74% (95% CI, 56%-87%) and the CR rate was 52% (95% CI, 39%-65%) in those who received 3 or more prior lines of treatment (n = 56).
Moreover, among those who were relapsed or refractory to their last prior therapy (n = 62), the CR rate was 52% (95% CI, 39%-65%) compared with 79% (95% CI, 59%-92%) in those who were not (n = 28). In patients who were double refractory (n = 48) the CR rate with the agent was 50% (95% CI, 35%-65%) vs 71% (95% CI, 55%-84%) in those who were not. In those with POD24 disease (n = 47), the CR rate with the agent was 57% (95% CI, 42%-72%) vs 63% (95% CI, 47%-77%) in those who did not have this disease (n = 43).
The median time to first response with mosunetuzumab was 1.4 months (range, 1.1-8.9). Moreover, the median time to first CR was 3.0 months (range, 1.1-18.9) with the agent.
All study participants reported toxicities; 92.2% of these patients experienced adverse effects (AEs) linked with the study treatment. Moreover, 70% of patients reported grade 3 or 4 toxicities, and 51.1% were related to mosunetuzumab. Serious AEs occurred in 46.7% of patients, and 33.3% of these effects were associated with the study drug. Two patients died but neither of these events were determined to be linked with mosunetuzumab.
Additionally, 44.4% of patients experienced cytokine release syndrome (CRS) with the bispecific antibody. Although these effects were primarily grade 1 (25.6%) or grade 2 (16.7%) in severity, 1 patient experienced grade 3 CRS and 1 had grade 4 CRS. All events resolved.
Of the 90 patients, 4 patients experienced toxicities that resulted in treatment discontinuation. Half of these patients (n = 2) discontinued due to an AE linked with mosunetuzumab.
Previously, in June 2020, mosunetuzumab received a breakthrough therapy designation from the FDA for use as a potential therapeutic option in adult patients with follicular lymphoma who previously received at least 2 systemic therapies.
Based on the positive opinion, the European Commission is expected to make a final decision regarding the conditional approval of the bispecific antibody in the near future, according to Roche.