The T-cell receptor therapy with afamitresgene autoleucel in advanced synovial sarcoma

Results from the phase II SPEARHEAD-1 trial, recently published on The Lancet, shows durable responses in heavily pre-treated patients with synovial sarcoma, indicating that T-cell receptor therapies can be used to effectively target solid tumours.

Afamitresgene autoleucel (afami-cel) is a medicinal product designed using a patient’s own T-cell genetically modified to produce a protein that attaches to MAGE-A4 via the HLA-A*02 protein found at the surface of the cancerous cells. Afami-cel showed acceptable safety and promising efficacy in a phase 1 trial and in January 2024 the FDA accepted the biologics license application for afami-cel for the treatment of patients with advanced synovial sarcoma for priority review. In the open-label, non-randomised, phase 2 trial SPEARHEAD-1 authors evaluated the efficacy of afami-cel for the treatment of patients with HLA-A*02 and MAGE-A4-expressing metastatic or unresectable synovial sarcoma or myxoid round cell liposarcoma. A total of 60 patients (52 with cytogenetically confirmed synovial sarcoma, 8 with myxoid round cell liposarcoma), who had received a medianof three previous lines of anthracycline-containing or ifosfamide-containing systemic chemotherapy, received a single intravenous dose of afami-cel after lymphodepletion. Overall response rate was 37% overall, 39% (17 of 44) for patients with synovial sarcoma and 25% (two of eight) for patients with myxoid round cell liposarcoma; cytopenias were the most common grade 3 or worse adverse events and no treatment-related death occurred. As the lead author Sandra D’Angelo from the Memorial Sloan Kettering Cancer Center in New York said «The reported findings are clinically impactful, considering the current standard of care and limited therapies available in advanced sarcomas. These results suggest that a one-time treatment with afami-cel has the potential to extend life while allowing responders to go off chemotherapy. Together, data from these phase 1 and 2 trials suggest that afami-cel can produce durable responses with an acceptable benefit-to-risk profile in HLA-eligible patients with MAGE-A4-expressing advanced synovial sarcoma. These data have been used to file for a biologics license application approval by the US Food and Drug Administration, which, if granted, would to our knowledge be the first approval of an engineered T-cell therapy for solid tumours».