FDA Grants Accelerated Approval to Mosunetuzumab-Axgb for Relapsed or Refractory Follicular Lymphoma
On December 22, 2022, the U.S. Food and Drug Administration (FDA) granted accelerated approval (https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-mosunetuzumab-axgb-relapsed-or-refractory-follicular-lymphoma) to mosunetuzumab-axgb (Lunsumio®), a bispecific, CD20-directed, CD3 T-cell engager for adult patients with relapsed or refractory follicular lymphoma (FL) who’ve received two or more lines of systemic therapy.
Mosunetuzumab-axgb was evaluated in GO29781 (NCT02500407), an open-label, multicenter, multicohort study. The efficacy population consisted of 90 patients with relapsed or refractory FL who received at least two prior lines of systemic therapy, including an anti-CD20 monoclonal antibody and an alkylating agent.
The main efficacy outcome measure was objective response rate (ORR) assessed by an independent review facility according to standard criteria for non-Hodgkin’s lymphoma (https://imaging.cancer.gov/clinical_trials/docs/Cheson%20(IWG)%20Criteria%20JCO%202007.pdf). The ORR was 80% (95% CI = 70, 88), with 60% achieving complete responses. After a median follow-up of 14.9 months among responders, the estimated median duration of response (DOR) was 22.8 months (95% CI = 10, not reached) and the estimated DOR rate at 12 months and 18 months was 62% and 57%, respectively.
The package insert has a boxed warning for serious or life-threatening cytokine release syndrome (CRS). It also contains warnings and precautions for neurologic toxicity, infections, cytopenias, and tumor flare. Among 218 patients with hematologic malignancies who received mosunetuzumab-axgb at the recommended dose, CRS occurred in 39%, neurologic toxicity in 39% (including immune effector cell-associated neurotoxicity syndrome in 1%), serious infections in 17%, and tumor flare in 4%. CRS was grade 2 in 15%, grade 3 in 2%, and grade 4 in 0.5%.
In the pooled safety population of 218 patients treated with mosunetuzumab-axgb, the most common adverse reactions reported in at least 20% were CRS, fatigue, rash, pyrexia, and headache. The most common grade 3–4 laboratory abnormalities reported in at least 10% of patients treated with mosunetuzumab-axgb were decreased lymphocyte count, decreased phosphate, increased glucose, decreased neutrophil count, increased uric acid, decreased white blood cell count, decreased hemoglobin, and decreased platelets.
The recommended mosunetuzumab-axgb dose is 1 mg 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 in subsequent cycles. A treatment cycle is 21 days. Administer mosunetuzumab-axgb for eight cycles or until patients experience unacceptable toxicity or disease progression. After eight cycles, patients with a complete response should discontinue therapy. Patients with a partial response or stable disease should continue treatment for up to 17 cycles or until they experience progressive disease or unacceptable toxicity.
View the full prescribing information for mosunetuzumab-axgb (https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/761263s000lbl.pdf).
The review used the Assessment Aid (https://www.fda.gov/about-fda/oncology-center-excellence/assessment-aid), a voluntary submission from the applicant to facilitate the FDA’s assessment.
The application was granted priority review and breakthrough designation. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics (https://www.fda.gov/regulatory-information/search-fda-guidance-documents/expedited-programs-serious-conditions-drugs-and-biologics). The application also was granted orphan drug designation.
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System (https://www.accessdata.fda.gov/scripts/medwatch/index.cfm) or by calling 800-FDA-1088.
For assistance with single-patient investigational new drug applications, contact OCE’s Project Facilitate (https://www.fda.gov/about-fda/oncology-center-excellence/project-facilitate) at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov (mailto:OncProjectFacilitate@fda.hhs.gov).