FDA Approves First Gene Therapy for Adults with Metastatic Synovial Sarcoma

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Tecelra (afamitresgene autoleucel), a first-of-its-kind gene therapy for the treatment of synovial sarcoma made by Adaptimmune, was approved by FDA on Aug. 2, 2024 for use in adults with an unresectable or metastatic case of this rare form of cancer and who have received prior chemotherapy, are positive for certain human leukocyte antigens (HLA), and whose tumor(s) may express melanoma-associated antigen (MAGE)-A4 as determined by a diagnostic device (1).

According to a press release from FDA, Tecelra is also the first FDA-approved T-cell receptor (TCR) gene therapy, an autologous immunotherapy composed of a patient’s own T cells, which are modified to express a TCR that targets MAGE-A4 (1). As an immune system trigger, that antigen is normally expressed by cancer cells in synovial sarcoma; among the other antigens for which Tecelra patients may be positive are HLA A*02:01P, -A*02:02P, -A*02:03P, and -A*02:06P.

Synovial sarcoma, which affects about 1000 people annually in the United States, most of them adult males under the age of 40, is a cancer in which malignant cells develop and form into a tumor in soft tissue, most often in the extremities, although it can be found in all parts of the body, and cancerous cells can spread throughout the body as well (1). It is treated with surgery to remove the tumor, followed by radiotherapy and/or chemotherapy if the tumor is large, has returned after being removed, or has metastasized.

“Adults with metastatic synovial sarcoma, a life-threatening form of cancer, often face limited treatment options in addition to the risk of cancer spread or recurrence,” said Nicole Verdun, MD, director of the Office of Therapeutic Products in FDA’s Center for Biologics Evaluation and Research (CBER), in the press release. “Today’s approval represents a significant milestone in the development of an innovative, safe, and effective therapy for patients with this rare but potentially fatal disease.”

FDA’s Accelerated Approval pathway provided Tecelra with an opportunity to be approved while Adaptimmune conducts further trials to verify the therapy’s predicted benefit, and one such confirmatory trial is currently ongoing (1). Accelerated Approval allows FDA to move certain drugs forward for treatment of conditions or diseases that are serious or life-threatening and have an unmet medical need, and for which the drugs’ effects on surrogate endpoints have been beneficial (2). In a multicenter, open-label clinical trial, Tecelra produced a response rate of 43.2% among 44 patients, with six months as the median duration of response, according to FDA.

“Potentially life-threatening cancers such as synovial sarcoma continue to have a devastating impact on individuals, especially those for whom standard treatments have limited efficacy due to tumor growth and progression,” said Peter Marks, MD, PhD, director of the CBER. “The approval of this state-of-the-art immunotherapy technology provides a critical new option for a patient population in need and demonstrates the FDA’s dedication to the advancement of beneficial cancer treatments.”

References

1. FDA. FDA Approves First Gene Therapy to Treat Adults with Metastatic Synovial Sarcoma. Press Release. Aug. 2, 2024.
2. FDA. Accelerated Approval. FDA.gov/patients, Feb. 24, 2023 (accessed Aug. 5, 2024).