Phase II SPEARHEAD-1 Trial Data Lead to FDA Priority Review for Novel T-Cell Therapy

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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