Multinational phase 2 trial of afamitresgene autoleucel for advanced synovial sarcoma and myxoid round cell liposarcoma

Afamitresgene autoleucel (afami-cel) is a CAR-T cell therapy with acceptable safety and promising efficacy for synovial sarcoma (SS) in a phase 1 trial. The multinational phase 2 SPEARHEAD trial evaluated afami-cel for heavily pretreated patients with HLA-A*02 and MAGE-A4-expressing metastatic or unresectable SS or myxoid round cell liposarcoma (MRCLS). Patients received a single intravenous dose of afami-cel after lymfodepletion. Primary endpoint was overall response rate. The overall response rate was 37% (95% CI 24-51); in SS patients the ORR was 39% (24-55) and in MRCLS patients the ORR was 25% (3-65). Cytokine release syndrome occurred in 71% of patients (one grade 3 event). Cytopenias were the most common grade 3 or worse adverse events. No treatment-related deaths occurred. The author conclude that afami-cel treatment resulted in durable responses in heavily pretreated patients with HLA-A*02 and MAGE-A4 expressing synovial sarcoma.