FDA Approval Summary: Afamitresgene Autoleucel for Adults With HLA-Restricted MAGE-A4 Positive Unresectable or Metastatic Synovial Sarcoma After Prior Chemotherapy.

Abstract

On August 1, 2024, the FDA granted accelerated approval to afamitresgene autoleucel, a melanoma-associated antigen-A4 (MAGE-A4)-directed genetically modified autologous T-cell immunotherapy, for the treatment of adults with unresectable or metastatic synovial sarcoma (SS) who have received prior chemotherapy, are HLA-A*02:01P, -A*02:02P, -A*02:03P, or -A*02:06P positive, and whose tumors express MAGE-A4 as determined by FDA-approved or cleared companion diagnostic devices. Approval was based on results from the phase 2, single-arm, open-label, multicenter Study ADP-0044-002. Patients received a single dose of afamitresgene autoleucel following lymphodepleting chemotherapy. Of the 44 efficacy evaluable patients, the overall response rate was 43.2% (95% CI: 28.4, 59.0), with complete response in two patients (4.5%). The median duration of response was 6.0 months (95% CI: 4.6, not reached [NR]) with a median follow-up of 21.9 months. Among the 44 patients, cytokine release syndrome occurred in 75% (Grade ≥3, 2%) warranting a Boxed Warning. Grade ≥3 infections occurred in 14% of patients and prolonged severe cytopenias also occurred. One patient developed Grade 1 immune effector cell-associated neurotoxicity and one patient developed Epstein-Barr virus-positive lymphoproliferative disease. Notably, during review of this application, FDA identified issues with data quality and study conduct that prompted an independent re-review of imaging assessments. The results of the re-review were the basis for FDA's determination of substantial evidence of effectiveness. This represents the first FDA approval of a T-cell receptor gene therapy. It is also the first FDA approval specifically for SS, representing a new treatment modality for this rare population who lack effective therapies.