First TCR T-cell Therapy Approved for Cancer
Afamitresgene autoleucel has received accelerated approval to treat certain patients with synovial sarcoma.
The U.S. Food and Drug Administration (FDA) has granted accelerated approval to afamitresgene autoleucel (Tecelra, afami-cel) for the treatment of certain adult patients with unresectable or metastatic synovial sarcoma who have received prior chemotherapy. Patients must also test positive for the HLA haplotype A*02:01P, A*02:02P, A*02:03P, or A*02:06P, and their tumors must express the protein MAGE-A4.
Afami-cel is a T-cell receptor (TCR) T-cell therapy, a type of cellular immunotherapy in which patients’ T cells are harvested, engineered to better fight their tumor, and infused back into the patient’s body. Afami-cel targets the protein MAGE-A4 on the surface of many solid tumors, including some synovial sarcomas.
Antigens like MAGE-A4 are presented to immune cells with the help of HLA proteins. Only certain HLA proteins can present MAGE-A4, so afami-cel is approved only for patients who have such an HLA.
This is the first approval for afami-cel, which is the first cellular immunotherapy approved for synovial sarcoma and the first TCR T-cell therapy to be approved for any cancer.
The approval was based on results from the multicenter, single-arm, open-label, phase II SPEARHEAD-1 clinical trial. Researchers enrolled 52 patients with unresectable or metastatic synovial sarcoma who had received prior chemotherapy, whose tumors expressed MAGE-A4, and who tested positive for certain HLA-A*02 haplotypes; 44 received a single infusion of afami-cel.
Overall, 43.2% of treated patients responded to afami-cel, with a median response duration of six months. Of these, 45.6% and 39% were still experiencing a response after six and 12 months, respectively.
The recommended dose of afami-cel is between 2.68×109 and 10×109 engineered T cells, without a leukodepletion filter or systemic corticosteroids.
The prescribing information for afami-cel includes a boxed warning for cytokine release syndrome, a potentially serious or fatal reaction of the immune system.
Synovial sarcoma is a rare type of soft tissue sarcoma often found near joints. According to the National Cancer Institute, 1 to 2 people per million are diagnosed each year in the United States.
The FDA rendered its decision on August 2, 2024. Accelerated approval means that continued approval may be contingent upon a confirmatory trial.
