FDA Grants Priority Review to BLA of Afami-cel in Synovial Sarcoma


Early data of afamitresgene autoleucel suggest substantial benefits for those with advanced synovial sarcoma who haven't responded to other treatments.

  • The FDA has expedited its review of afamitresgene autoleucel (afami-cel), a novel engineered T-cell therapy, for treating patients with advanced synovial sarcoma.

  • This decision comes based on encouraging results from the ongoing SPEARHEAD-1 trial (NCT04044768).

  • The FDA's target date for a decision on afami-cel's approval is August 4, 2024.

The biologics license application (BLA) seeking the approval of afami-cel, an investigational engineered T-cell therapy, has been accepted for priority review by the FDA for patients with advanced synovial sarcoma.1

This decision comes based on encouraging results from the ongoing SPEARHEAD-1 trial. Data from cohort 1 of the phase 2 study were presented at the 2023 Connective Tissue Oncology Society (CTOS) Annual Meeting in Dublin, Ireland, and showed that approximately 39% of patients with heavily pretreated synovial sarcoma responded to afami-cel, with a median duration of response of approximately 12 months.2,3

The median overall survival was approximately 17 months among patients in cohort 1. Patients who responded to afami-cel treatment also had a 70% chance of being alive at 2 years post-treatment, suggesting the potential long-term impact of the agent.2

The FDA set The Prescription Drug User Fee Act target action date for a decision on afami-cel's approval for August 4, 2024. If approved, it would represent a significant advancement in the in the treatment of patients with synovial sarcoma.

“The FDA’s acceptance of the BLA submission brings us one step closer to redefining treatment for [patients] with synovial sarcoma,” said Adrian Rawcliffe, chief executive officer of Adaptimmune Therapeutics’, in a press 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.”

Tumor microenvironment background with cancer cells, T-Cells, nanoparticles, molecules, and blood vessels. Oncology research concept: © ratatosk - stock.adobe.com

Tumor microenvironment background with cancer cells, T-Cells, nanoparticles, molecules, and blood vessels. Oncology research concept: © ratatosk - stock.adobe.com

Afami-cel is an engineered T-cell receptor therapy which works to target the MAGE-A4 protein among patients with synovial sarcoma. This type of sarcoma makes up about 5%-10% of all soft tissue sarcomas, with around 13,400 new cases diagnosed each year in the United States.2 The outlook for patients with synovial sarcoma often is poor, with only 20% of patients survival for 5 years after diagnosis, often due to recurrence among patients with advanced disease and the limitedtreatment options available.2

The T-cell therapy offers hope for this patient population as early results show that the therapy can be effective in targeting and killing cancer cells. This could lead to improved survival rates and treatment options for people with synovial sarcoma.

SPEARHEAD-1 is a single-arm, open-label, phase 2 trial which enrolled patients with a diagnosis of advanced synovial sarcoma or myxoid liposarcoma/myxoid round cell liposarcoma who were over the age of 16 into cohort 1 of the trial. To be eligible for inclusion, patients must have measurable disease, have received prior treatment with an anthracycline or ifosfamide-containing regimen, and have an ECOG performance status of 0 or 1.3 Further, patients must have tested positive for HLA-A*02:01, HLA-A*02:02, HLA-A*02:03, or HLA-A*02:06, and have MAGE-A4 expression of 1 or greater staining in at least 10% of cells by immunohistochemistry.

The primary end point was overall response rate (ORR) with secondary end points of treatment-related adverse events, safety, measurement of T-cell clonality and insertional oncogenesis in peripheral blood mononuclear cells (PBMCs), best overall response, time to response, duration of response, progression-free survival, overall survival, quantitation of genetically engineered T-cells in PBMCs, time taken to achieve peak expansion of genetically engineered T-cells in PBMCs by flow cytometry, and in vitro diagnostic assay for screening.

The study treated approximately 90 patients who were evenly split into cohorts 1 and 2. With the main efficacy analysis focused on cohort 1, cohort 2 of the study aims to enhance the efficacy and safety data and will contribute to descriptive subgroup analyses.

According to a press release, the ORR for cohort 2 of the trial is similar with that observed in cohort 1. Specific data will be shared once follow-up is complete.2 Further, cohort 3 of the study is now enrolling patients.

“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 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. 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. http://tinyurl.com/ycxaztmn
  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. http://tinyurl.com/5dt6b9sj
  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
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