FDA Grants Afami-cel Accelerated Approval in Advanced Synovial Sarcoma

• The FDA has granted an accelerated approval to Tecelra (afamitresgene autoleucel; afami-cel) for treating patients with advanced synovial sarcoma.
• Afami-cel is a novel engineered T-cell therapy that targets the MAGE-A4 protein among patients with synovial sarcoma.
• Findings from the SPEARHEAD-1 trial (NCT04044768) support this regulatory decision.

The FDA has granted afami-cel, an engineered T-cell receptor therapy which works to target the MAGE-A4 protein, an accelerated approval for the treatment of patients with advanced synovial sarcoma.¹

Findings from cohort 1 of the phase 2 SPEARHEAD-1 trial support this regulatory decision. Data from the study presented at the 2023 Connective Tissue Oncology Society (CTOS) Annual Meeting in Dublin, Ireland, showed that approximately 39% of patients with heavily pretreated synovial sarcoma responded to afami-cel. The median duration of response was approximately 12 months, and the median overall survival was approximately 17 months in this cohort.^2,3

Of the responders to treatment with afami-cel, 70% have a chance of being alive at 2 years post-treatment. These results suggest the potential long-term impact of the agent.²

“For synovial sarcoma, this is super important and a practice-changing approval,” Sandra P. D'Angelo, MD, a medical oncologist at Memorial Sloan Kettering Cancer Center, told Targeted Oncology^TM in an interview. “Afami-cel offers a remarkable improvement upon the standard –of care, so it is a promising and exciting option for our patients. It also provides a lot of hope and excitement for patients with rare cancers as it shows the ability of our sarcoma community to work together to identify these patients, treat these patients, and bring this drug over the finish line.”

A medical illustration featuring cancer cells from a microscopic to macroscopic view, illuminated by neon lights to enhance visual clarity and focus: © Fay Melronna - stock.adobe.com

About SPEARHEAD-1

The single-arm, open-label, phase 2 SPEARHEAD-1 study included 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.³

Enrollment was open to patients with measurable disease who have received prior treatment with an anthracycline- or ifosfamide-containing regimen and have an ECOG performance status of 0 or 1. Patients were required to 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.

Investigators evaluated the primary end point of overall response rate and the 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.

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

REFERENCES:

1. Adaptimmune receives U.S. FDA accelerated approval of TECELRA® (afamitresgene autoleucel), the first approved engineered cell therapy for a solid tumor. News release. Adaptimmune. August 1, 2024. Accessed August 1, 2024. https://tinyurl.com/tch2emrw

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 July 8, 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 July 8, 2024. https://classic.clinicaltrials.gov/ct2/show/NCT04044768