First gene engineered T-cell therapy for solid tumours confirmed to be a promising tool

On August 2, 2024, the FDA granted accelerated approval to afamitresgene autoleucel, marking the first gene-engineered T-cell therapy approved for the treatment of solid tumors. This therapy is specifically designed for adults with unresectable or metastatic synovial sarcoma, a rare and aggressive cancer with limited treatment options.

Promising Results from the SPEARHEAD-1 Trial

The approval was based on the positive outcomes of the phase 2 SPEARHEAD-1 trial, which evaluated the efficacy and safety of afamitresgene autoleucel in 52 patients with synovial sarcoma or myxoid round cell liposarcoma. These cancers account for 5-10% of all soft tissue sarcomas and typically have poor responses to existing second-line treatments.

All patients in the trial had tumors expressing the melanoma-associated antigen A4 (MAGE-A4) and were positive for specific HLA-A*02 alleles. The therapy involves genetically modifying a patient’s own T cells to target and destroy cancer cells expressing MAGE-A4.

Durable Responses with Manageable Toxicities

The trial reported an overall response rate (ORR) of 37%, with a 39% response rate in patients with synovial sarcoma and 25% in those with myxoid round cell liposarcoma. The median duration of response was 6 months, and nearly half of the responding patients maintained their response for at least 6 months.

While hematological toxicities were common due to lymphodepletion chemotherapy, they were generally manageable. The most frequent adverse event was cytokine release syndrome, but most cases were mild and treatable.

A Milestone in Personalized Cancer Therapy

The approval of afamitresgene autoleucel represents a significant advancement in personalized medicine, particularly for solid tumors. This therapy paves the way for further innovations in cancer treatment, offering new hope to patients with limited options.