Afami-cel Granted Accelerated Approval for Advanced Synovial Sarcoma

The FDA granted accelerated approval to afamitresgene autoleucel (afami-cel), an engineered T-cell receptor therapy targeting the MAGE-A4 protein, for the treatment of advanced synovial sarcoma.¹ Afami-cel, sold as Tecelra by Adaptimmune, is the first gene therapy to be approved for the rare form of cancer and the first FDA-approved T-cell receptor (TCR) gene therapy.²

The accelerated approval was based on safety and efficacy data from the multicenter, open-label, phase 2 SPEARHEAD-1 trial (NCT03132922), which showed positive overall response rates and duration of response among patients treated with afami-cel.¹ As with all drugs greenlit under the accelerated approval pathway, afami-cel’s continued approval may be contingent on confirmatory trials.

Synovial sarcoma is a rare type of soft tissue sarcoma impacting approximately 1000 individuals in the US yearly.² While it can occur in various areas of the body, it most commonly manifests in extremities. Afami-cel is indicated for adult patients with unresectable or metastatic synovial sarcoma following prior chemotherapy, who are positive for HLA antigen(s) A*02:01P, -A*02:02P, -A*02:03P, or -A*02:06P, and with MAGE-A4 antigen expression as determined by FDA-authorized diagnostics.

“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,” Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research (CBER), said in a statement. “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.”

Standard therapy for synovial sarcoma entails tumor resection as well as radiotherapy and/or chemotherapy when tumors are large, recurring, or spreading from their original location. Afami-cel, which is administered in a single intravenous dose, is an autologous TCR therapy comprising the patient’s own T cells, which are modified to express a TCR targeting MAGE-4.

Findings from the SPEARHEAD-1 trial published in The Lancet demonstrated durable responses in heavily pretreated patients with HLA-A*02 and MAGE-A4–expressing synovial sarcoma at a median follow-up of 32.6 months (IQR, 29.4-36.1).³ Patients with confirmed synovial sarcoma (n = 44) or myxoid round cell liposarcoma (n = 8) who received the gene therapy after a median of 3 (IQR, 2-4) lines of prior systemic therapy experienced an overall response rate (ORR) of 37% (95% CI, 24-51). Among patients with synovial sarcoma, the ORR was 39% (95% CI, 24-55).

Regarding adverse events (AEs), 71% of patients experienced cytokine release syndrome, one case being grade 3. The most common grade 3 or worse AEs were cytopenias, including lymphopenia, neutropenia, and leukopenia. There were no treatment-related deaths reported.

A confirmatory trial to verify the benefits of afarmi-cel is ongoing.²

“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 CBER. “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.”

References

1. Adaptimmune receives U.S. FDA accelerated approval of Tecelra (afamitresgene autoleucel), the first approved engineered cell therapy for a solid tumor. News release. Adaptimmune Therapeutics. August 1, 2024. Accessed August 2, 2024. https://www.businesswire.com/news/home/20240801538240/en/Adaptimmune-Receives-U.S.-FDA-Accelerated-Approval-of-TECELRA%C2%AE-afamitresgene-autoleucel-the-First-Approved-Engineered-Cell-Therapy-for-a-Solid-Tumor

2. FDA Approves First Gene Therapy to Treat Adults with Metastatic Synovial Sarcoma. News release. FDA. August 2, 2024. Accessed August 2, 2024. https://www.fda.gov/news-events/press-announcements/fda-approves-first-gene-therapy-treat-adults-metastatic-synovial-sarcoma

3. D'Angelo SP, Araujo DM, Abdul Razak AR, et al. Afamitresgene autoleucel for advanced synovial sarcoma and myxoid round cell liposarcoma (SPEARHEAD-1): an international, open-label, phase 2 trial. Lancet. 2024;403(10435):1460-1471. doi:10.1016/S0140-6736(24)00319-2