Adaptimmune Submits Afami-Cel First Engineered TCR-T Therapy BLA for Synovial Sarcoma


The cell therapy yielded a median overall survival of around 17 months compared with a historical OS of less than 12 months.

Brian Van Tine, MD, PhD

Brian Van Tine, MD, PhD

Adaptimmune Therapeutics has submitted its Biologics License Application (BLA) for afami-cel (afamitresgene autoleucel) T-cell receptor (TCR) T-cell therapy for treating synovial sarcoma (SS).1

"Synovial sarcoma is a rare tumor most commonly affecting young adults between the ages of 15 and 40 that arises from a chromosomal translocation between chromosomes X and 18. The therapeutic options for synovial sarcoma are limited to intense chemotherapy regiments and tyrosine kinase inhibitors," investigator Brian Van Tine, MD, PhD, professor, medicine and pediatrics, Washington University in St. Louis, told CGTLive. "With the BLA submission for afami-cel from Adaptimmune, there is hope for a T-cell therapy for Synovial Sarcoma patients that are both HLA:02 and MAGEA4 positive. Responders on the phase 2 clinical trial had a durable response that lasted greater than a year from a single treatment. It is my hope that this therapy get improved and we continue to advance options for patients with rare tumors."

The submission is the first BLA for an engineered T-cell therapy for solid tumors submitted to the FDA. Afami-cel is eligible for a priority review. The therapy is targeted to the MAGE-A4 antigen. The FDA has previously granted it Orphan Drug Designation (ODD) for the treatment of soft tissue sarcomas and Regenerative Medicine Advanced Therapy (RMAT) designation for the treatment of synovial sarcoma. Synovial sarcoma accounts for approximately 5% to 10% of all soft tissue sarcomas.

WATCH NOW: Brian Van Tine, MD, PhD, on Looking Ahead on Cell Therapy for Sarcomas

"I celebrate the promise that breakthrough therapies like afami-cel offer to sarcoma patients. Such advancements offer hope and transformative possibilities for the sarcoma patient community, addressing critical unmet needs and offering increased and improved treatments for people diagnosed with sarcoma. I am hopeful for and excited about a new treatment choice for people diagnosed with synovial sarcoma,” Brandi Felser, chief executive officer, Sarcoma Foundation of America, said in a statement.1

The BLA submission is supported by positive data from Cohort 1 of the pivotal SPEARHEAD-1 trial (NCT04044768), which met its primary efficacy endpoint of overall objective response (ORR) compared to natural history. Adaptimmune previously announced data from the trial that showed a 39% ORR and a median duration of response of around 12 months. Median overall survival (OS) was around 17 months compared with a historical median OS of less than 12 months in patients with SS that have received at least 2 prior lines of therapy. Patients in SPEARHEAD-1 had a median of 3 prior lines of systemic therapy (range, 1-12). Of responders in the trial, 70% are alive 2 years after treatment. Median time to next treatment, a measure correlated with OS in metastatic sarcoma, was around 7 months overall and around 17 months in responders in the trial compared with 6, 3, or 2 months historically after 2, 3, or 4 lines of prior systemic therapy.2

Investigators in SPEARHEAD-1 also found that higher afami-cel cellular persistence was associated with longer OS. The therapy showed a manageable safety profile in line with previous findings including cytokine release syndrome and reversible hematologic toxicities.

"With this submission, we have completed a critical step toward making cell therapy a mainstream treatment option for people with solid tumors. I would like to thank the trial participants and clinical trial investigators, the synovial sarcoma community, and our afami-cel team for their diligent efforts in completing the BLA submission,” Adrian Rawcliffe, chief executive officer, Adaptimmune, added to the statement.1 “We look forward to continued collaboration with the FDA as they review the first ever application for marketing approval for an engineered T-cell therapy for solid tumors. We continue to prepare for the commercial launch of afami-cel and the evolution of our sarcoma cell therapy franchise, which now includes lete-cel."

1. Adaptimmune completes submission of rolling biologics license application (BLA) to U.S. FDA for afami-cel for the treatment of advanced synovial sarcoma. News release. Adaptimmune. December 6, 2023.
2. Adaptimmune reports better outcomes for people with synovial sarcoma who received afami-cel compared to historical Control. News release. Adaptimmune. October 31, 2023.
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