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The FDA has granted Priority Review status to Adaptimmune Therapeutics’ biologics license application (BLA) for afamitresgene autoleucel (afami-cel) in the treatment of advanced synovial sarcoma. The BLA for the novel engineered T-cell therapy was assigned a Prescription Drug User Fee Act target action date of August 4, 2024.1
“The FDA’s acceptance of the BLA submission brings us one step closer to redefining treatment for people with synovial sarcoma,” Adaptimmune CEO Adrian Rawcliffe said in a press release. “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.”1
Afami-cel, an engineered T-cell receptor drug, was developed to target the MAGE-A4 protein in synovial sarcoma, which comprises 5% to 10% of soft tissue sarcomas. There are approximately 13,400 new soft tissue sarcoma cases reported annually in the United States, which have limited treatment options.2 The five-year survival rate among patients with metastatic synovial sarcoma is 20%, with recurrence common among those with advanced disease.2
The BLA submission was based on findings from the Phase II SPEARHEAD-1 trial (NCT04044768).1,2 The trial data show that treatment with afami-cel produced an overall response rate of about 39% in patients with heavily pretreated synovial sarcoma in cohort 1 of the ongoing trial. Median duration of response with afami-cel was about 12 months, showing the durability of the treatment, according to the study investigators.2 Median overall survival was approximately 17 months in cohort 1.
Investigators estimate that those who respond to treatment with afami-cel have a 70% chance of being alive at two years following treatment.2
Cohort 1 of SPEARHEAD-1 enrolled patients over 16 years of age with advanced synovial sarcoma or myxoid liposarcoma/myxoid round cell liposarcoma. Enrollment criteria included prior treatment with an anthracycline or ifosfamide-containing regimen; measurable disease; positive testing for HLA-A*02:01, HLA-A*02:02, HLA-A*02:03, or HLA-A*02:06; MAGE-A4 expression of one 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 split between cohorts 1 and 2, with the primary efficacy analysis in cohort 1, whereas cohort 2 contributed to descriptive subgroup analyses, as well as efficacy and safety data. Adaptimmune stated that the overall response rate among both cohorts was similar.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,” said Dennis Williams, PharmD, senior vice president of Late-Stage Development at Adaptimmune Therapeutics, in a press release. “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
References
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 2, 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 2, 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 2, 2024. https://classic.clinicaltrials.gov/ct2/show/NCT04044768