FDA D.I.S.C.O. Burst Edition: FDA approval of Tecelra (afamitresgene autoleucel) for unresectable or metastatic synovial sarcoma

Regulatory approval: On Aug 2, 2024, the FDA granted accelerated approval to Tecelra (afamitresgene autoleucel), a MAGE-A4–directed genetically modified autologous T-cell immunotherapy, for certain adults with unresectable or metastatic synovial sarcoma after prior chemotherapy. Eligibility includes specific HLA-A*02 alleles and MAGE-A4–positive tumors identified by FDA-approved/cleared companion diagnostics. In SPEARHEAD-1 Cohort 1 (single-arm), overall response rate was 43.2% with median duration of response 6 months. Label includes a boxed warning for serious or fatal cytokine release syndrome.

FDA accelerated approval (Aug 2, 2024): Tecelra for synovial sarcoma

The FDA granted accelerated approval on August 2, 2024 to Tecelra (afamitresgene autoleucel), a melanoma-associated antigen A4 (MAGE-A4)–directed genetically modified autologous T-cell immunotherapy, for adults with unresectable or metastatic synovial sarcoma who:

  • have received prior chemotherapy;
  • are HLA-A*02:01P, -A*02:02P, -A*02:03P, or -A*02:06P positive; and
  • have tumors that express MAGE-A4, as determined by FDA-approved or cleared companion diagnostic devices.

Supporting clinical evidence

Efficacy was evaluated in SPEARHEAD-1, Cohort 1, a multicenter, single-arm, open-label trial enrolling HLA-A*02:01–03 and 06 allele–positive patients with inoperable or metastatic synovial sarcoma who had received prior systemic therapy with doxorubicin and/or ifosfamide and had MAGE-A4–expressing tumors. Patients received lymphodepleting chemotherapy with fludarabine and cyclophosphamide.

  • Primary endpoint: overall response rate (ORR) per RECIST v1.1 by independent review, supported by duration of response (DOR)
  • ORR: 43.2%
  • Median time to response: 4.9 weeks
  • Median DOR: 6 months
  • Among responders, 45.6% had DOR ≥6 months and 39.0% had DOR ≥12 months.

Safety

Prescribing information includes a Boxed Warning for serious or fatal cytokine release syndrome.

FDA noted use of an Assessment Aid (voluntary applicant submission) to facilitate review.

Sources