FDA grants accelerated approval to afamitresgene autoleucel for unresectable or metastatic synovial sarcoma
Regulatory approval: On Aug 2, 2024, the FDA granted accelerated approval to afamitresgene autoleucel (TECELRA), a MAGE-A4–directed genetically modified autologous T-cell immunotherapy, for adults with unresectable or metastatic synovial sarcoma after prior chemotherapy, who are HLA-A*02:01P/-A*02:02P/-A*02:03P/-A*02:06P positive and whose tumors express MAGE-A4 per FDA-approved/cleared companion diagnostics. Approval was supported by the single-arm SPEARHEAD-1 Cohort 1 trial (ORR 43.2%).
FDA accelerated approval: afamitresgene autoleucel (TECELRA) in synovial sarcoma
Type: Regulatory approval (accelerated approval)
Date: 2024-08-02
Agency: FDA
On August 2, 2024, the FDA granted accelerated approval to afamitresgene autoleucel (TECELRA; Adaptimmune, LLC), a MAGE-A4–directed genetically modified autologous T-cell immunotherapy, for adults with unresectable or metastatic synovial sarcoma who have received prior chemotherapy, are HLA-A02:01P, -A02:02P, -A02:03P, or -A02:06P positive, and whose tumor expresses MAGE-A4 as determined by FDA-approved or cleared companion diagnostic devices.
Supporting efficacy evidence
Efficacy was evaluated in SPEARHEAD-1, Cohort 1, a multicenter, single-arm, open-label trial in HLA-A*02:01–03 and 06 allele–positive patients with inoperable/metastatic synovial sarcoma previously treated with systemic therapy (doxorubicin and/or ifosfamide) and with MAGE-A4–expressing tumors. Patients received lymphodepleting fludarabine and cyclophosphamide.
Of 52 leukapheresed patients, 44 received a single TECELRA infusion. The primary endpoint was ORR by independent review (RECIST v1.1), with DOR support: ORR 43.2% (95% CI, 28.4–59.0); median time to response 4.9 weeks; median DOR 6 months (95% CI, 4.6–not reached).
Safety and postmarketing
Labeling includes a Boxed Warning for serious or fatal cytokine release syndrome (CRS). The FDA noted a postmarketing requirement for an ongoing study to verify clinical benefit, consistent with accelerated approval.