The FDA has granted accelerated approval to mosunetuzumab-axgb (Lunsumio™, Genentech) for adult patients with relapsed or refractory follicular lymphoma (FL) who have previously received at least two lines of systemic therapy.
"Mosunetuzumab is a CD20 x CD3 T-cell–engaging bispecific monoclonal antibody that redirects T cells to eliminate malignant B cells," wrote L. Elizabeth Budde, MD, PhD, Associate Professor in the Department of Hematology & Hematopoietic Cell Transplantation at City of Hope in Duarte, California, and colleagues, in their published results of the GO29781 study (NCT02500407), on which the approval was based. "In a phase 1 study, mosunetuzumab was well tolerated and active in patients with relapsed or refractory B-cell lymphoma. We, therefore, aimed to evaluate the safety and anti-tumor activity of fixed-duration mosunetuzumab in patients with relapsed or refractory FL who had received two or more previous therapies."
The efficacy population of the open-label, multicenter, multi-cohort phase 2 trial consisted of 90 patients with relapsed/refractory FL who had received two or more prior systemic therapies, including an anti-CD20 monoclonal antibody and an alkylating agent. Patients received 1 mg of intravenous mosunetuzumab on Cycle 1, Day 1; 2 mg on Cycle 1, Day 8; 60 mg on Cycle 1, Day 15; 60 mg on Cycle 2, Day 1; and 30 mg on Day 1 of each cycle thereafter.
The primary end point was objective response rate according to standard criteria for non-Hodgkin lymphoma. Mosunetuzumab produced an objective response rate of 80%, with 60% of patients experiencing a complete response. At a median follow-up of 14.9 months among those who responded, the estimated median duration of response was 22.8 months. The estimated duration of response rate was 62% at 12 months and 57% at 18 months.
In a pooled safety population of 218 patients with hematologic malignancies who received the recommended dose of mosunetuzumab, the most common adverse events occurring in ≥20% of patients were cytokine release syndrome (CRS), fatigue, rash, pyrexia, and headache. Grade 3 or 4 laboratory abnormalities occurring in ≥10% of patients included decreased lymphocyte count, decreased phosphate, increased glucose, decreased neutrophil count, increased uric acid, decreased white blood cell count, decreased hemoglobin, and decreased platelets.
The prescribing information for mosunetuzumab contains a Boxed Warning for serious or life-threatening CRS, including neurologic toxicity, infections, cytopenias, and tumor flare. In the pooled safety population of 218 patients, 39% experienced CRS, including 15% grade 2, 2% grade 3, and 0.5% grade 4. Neurologic toxicity occurred in 39% of patients, including immune effector–cell associated neurotoxicity syndrome (ICANS) in 1%. Serious infections and tumor flare were experienced by 17% and 4% of patients, respectively.
"Fixed-duration mosunetuzumab has a favorable safety profile and induced high rates of complete remissions, allowing potential administration as an outpatient regimen, in patients with relapsed or refractory FL and two or more previous therapies," concluded Dr. Budde and colleagues in their publication in Lancet Oncology.
The recommended dose of mosunetuzumab is 1 mg on Cycle 1, Day 1; 2 mg on Cycle 1, Day 8; 60 mg on Cycle 1, Day 15; and 30 mg on Day 1 of each subsequent 21-day cycle. Patients should receive mosunetuzumab for eight cycles unless they experience disease progression or unacceptable toxicity. Those who achieve a complete response should discontinue therapy after completing eight cycles. Patients who have a partial response or stable disease should continue mosunetuzumab for up to 17 cycles unless they experience disease progression or unacceptable toxicity.
For More Information
Budde LE, Sehn LH, Matasar M, et al (2022). 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, 23(8):1055-1065. DOI:10.1016/S1470-2045(22)00335-7
Clinicaltrials.gov (2022). A safety, efficacy and pharmacokinetic study of BTCT4465A (mosunetuzumab) as a single agent and combined with atezolizumab in non-Hodgkin's lymphoma (NHL) and chronic lymphocytic leukemia (CLL). NLM identifier: NCT02500407.
Lunsumio™ (mosunetuzumab-axgb) prescribing information (2022). Genentech. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/761263s000lbl.pdf
US Food & Drug Administration (2022). FDA grants accelerated approval to mosunetuzumab-axgb for relapsed or refractory follicular lymphoma. Available at: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-mosunetuzumab-axgb-relapsed-or-refractory-follicular-lymphoma
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