FDA Grants Priority Review to Afami-Cel BLA in Advanced Synovial Sarcoma


The FDA has accepted for priority review the BLA seeking the approval of afamitresgene autoleucel for the treatment of advanced synovial sarcoma.



The FDA has accepted for priority review the biologics license application (BLA) seeking the approval of afamitresgene autoleucel (afami-cel), an investigational engineered T-cell therapy, for the treatment of patients with advanced synovial sarcoma. The Prescription Drug User Fee Act target action date for the application is August 4, 2024.1

The regulatory agency accepted the BLA based on data from cohort 1 of the phase 2 SPEARHEAD-1 trial (NCT04044768), which were presented at the 2023 Connective Tissue Oncology Society (CTOS) Annual Meeting in Dublin, Ireland.1,2 Previous results from the trial, which were presented at the 2022 CTOS meeting, showed that patients with heavily pretreated synovial sarcoma had an overall response rate of approximately 39% when treated with afami-cel. Moreover, the median duration of response with the agent was approximately 12 months, indicating the agent’s durability.2

Furthermore, the median overall survival of patients in cohort 1 of the ongoing study was approximately 17 months and it was estimated that patients who respond to afami-cel have a 70% chance of being alive at 2 years post-treatment.2

“The FDA’s acceptance of the BLA submission brings us one step closer to redefining treatment for [patients] with synovial sarcoma,” Adaptimmune Therapeutics’ chief executive officer, Adrian Rawcliffe, stated in the news release.1 “Our franchise has great potential and, if approved, we have the capabilities and the capital to launch afami-cel–the first engineered T-cell therapy on the market for a solid tumor cancer.”

The engineered T-cell receptor therapy was designed to target the MAGE-A4 protein in patients with synovial sarcoma, which constitutes 5% to 10% of soft tissue sarcomas, with approximately 13,400 new soft tissue cases annually in the United States.2 Furthermore, the 5-year survival rate for patients with metastatic synovial sarcoma is 20%. Recurrence is common among patients with advanced disease, and treatment options are limited.2

In the SPEARHEAD-1 trial, patients over the age of 16 with a diagnosis of advanced synovial sarcoma or myxoid liposarcoma/myxoid round cell liposarcoma were enrolled into cohort 1 of the trial. These patients had to have been previously treated with an anthracycline or ifosfamide-containing regimen; have measurable disease; test positive for HLA-A*02:01, HLA-A*02:02, HLA-A*02:03, or HLA-A*02:06; have MAGE-A4 expression of 1 or greater staining in at least 10% of cells by immunohistochemistry; and an ECOG performance status of 0 or 1.3

Approximately 90 patients were anticipated to be treated overall, evenly split into cohorts 1 and 2. At the time of the October 2023 press release, Adaptimmune announced that enrollment in both cohorts was complete.2 The main efficacy analysis is focused on cohort 1. Cohort 2, while enhancing the efficacy and safety data, will also contribute to descriptive subgroup analyses. According to the company, the overall response rate for cohort 2 closely mirrors that of cohort 1 and specific data will be shared once follow-up is complete.2

Cohort 3 is now open for enrollment to provide access to afami-cel ahead of planned commercialization.2

“Historic outcomes are poor for advanced synovial sarcoma, with low objective response rates for second-line therapies and overall survival of less than 12 months for [patients] who have received 2 or more prior lines of therapy,” Dennis Williams, PharmD, senior vice president of Late-Stage Development, Adaptimmune Therapeutics, said. “In clinical trials, afami-cel has demonstrated an impressive response rate of [approximately] 39% among heavily pretreated patients with advanced synovial sarcoma and about a 17-month median survival. This regulatory milestone is a testament to our teams’ relentless work to deliver a novel treatment option to more people diagnosed with synovial sarcoma.”


  1. Adaptimmune announces U.S. FDA acceptance of biologics license application for afami-cel for the treatment of advanced synovial sarcoma with priority review. News release. Adaptimmune. January 31, 2024. Accessed February 1, 2024. https://www.adaptimmune.com/ adaptimmune-announces-u-s-fda-acceptance-of-biologics
  2. Adaptimmune reports better outcomes for people with synovial sarcoma who received afami-cel compared to historical control. News release. Adaptimmune. October 31, 2023. Accessed February 1, 2024. https://www.adaptimmune.com/investors-and-media/news-center/press-releases/detail/253/adaptimmune-reports-better-outcomes-for-people-with
  3. Spearhead 1 study in subjects with advanced synovial sarcoma or myxoid/round cell Liposarcoma. ClinicalTrials.gov. Updated August 15, 2023. Accessed February 1, 2024. https://classic.clinicaltrials.gov/ct2/show/NCT04044768
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