FDA Approves First T-Cell Receptor Gene Therapy for Solid Tumors

The Food and Drug Administration granted accelerated approval on Friday to afamitresgene autoleucel (afami-cel), a T-cell receptor (TCR) gene therapy, to treat certain adult patients with unresectable or metastatic synovial sarcoma.

Afami-cel is the first FDA-approved engineered cell therapy for a solid tumor. It is indicated for adult patients who have received prior chemotherapy, are HLA-A*02:01P, -A*02:02P, -A*02:03P, or -A*02:06P positive, and whose tumor expresses the MAGE-A4 antigen as determined by FDA-approved or cleared companion diagnostic devices.

Marketed as Tecelra (Adaptimmune, LLC), afami-cel is an autologous T-cell product engineered with a self-inactivating lentiviral vector to express a high-affinity MAGE-A4-specific T-cell receptor. MAGE-A4 is expressed in solid tumors, including soft tissue sarcomas like synovial sarcoma.

FDA based its approval on findings from the SPEARHEAD-1 trial. Among the 44 patients in the trial who received afami-cel, the overall response rate was 43.2% and the median duration of response was six months. Among patients who were responsive to the treatment, 45.6% and 39% had a duration of response greater than or equal to six months and 12 months, respectively.

The prescribing information includes a boxed warning for serious or fatal cytokine release syndrome, which may be severe or life-threatening. To verify the clinical benefit of afami-cel, FDA and the sponsor agreed upon a postmarketing requirement for an ongoing study in this patient population.

This application also received Regenerative Medicine Advanced Therapy, priority review and orphan drug designations.