By Don Tracy, Associate Editor

Regulatory action marks the first engineered cell therapy approved for a solid tumor cancer in the United States.The FDA has granted accelerated approval to Adaptimmune Therapeutics’ Tecelra (afamitresgene autoleucel), an engineered cell therapy that targets resectable or metastatic synovial sarcoma in adults who have undergone prior chemotherapy and are HLA-A*02 positive with MAGE-A4 antigen expression. The treatment, which was approved based on results from the SPEARHEAD-1 trial, marks the first engineered cell therapy for a solid tumor cancer to be approved in the United States, according to the company.1
“The approval of Tecelra is a momentous step in Adaptimmune’s journey to redefine the way cancer is treated and the culmination of a decade of groundbreaking R&D. I want to thank the patients, caregivers, investigators, and clinical teams as well as everyone at Adaptimmune and our partners who made possible this watershed moment for cell therapy and for people with synovial sarcoma. We are committed to advancing our robust clinical pipeline to serve more patients in need and plan to progress lete-cel, the next late-stage investigational treatment in our sarcoma franchise, with a rolling BLA submission to the FDA next year,” said Adrian Rawcliffe, CEO, Adaptimmune Therapeutics, in a press release.
The open-label, non-randomized, Phase II SPEARHEAD-1 trial was conducted across 23 sites in Canada, the United States, and Europe. Consisting of three cohorts, Cohort 1 included patients with HLA-A*02, aged 16–75 years, with metastatic or unresectable synovial sarcoma or myxoid round cell liposarcoma, expressing MAGE-A4, and received at least one previous line of anthracycline- or ifosfamide-containing chemotherapy. Cohort 1 patients received a single intravenous dose of afami-cel (transduced dose range 1·0 × 109–10·0 × 109 T cells) after lymphodepletion.2
Results demonstrated an overall response rate of 43% and a complete response rate of 4.5%. Additionally, the median duration of response was six months, with 39% of responders maintaining their response for 12 months or longer. Full data from SPEARHEAD-1 was published in The Lancet earlier in the year.
Adaptimmune warned that Tecelra can cause serious adverse events (AEs), such as cytokine release syndrome (CRS), immune effector cell–associated neurotoxicity syndrome, prolonged severe cytopenia, infections, secondary malignancies, and hypersensitivity reactions. Common AEs included CRS, nausea, vomiting, fatigue, infections, pyrexia, constipation, dyspnea, abdominal pain, non-cardiac chest pain, decreased appetite, tachycardia, back pain, hypotension, diarrhea, edema, low white blood cells, low red blood cells, and low platelets.1
“For decades, therapeutic options for people diagnosed with synovial sarcoma have been limited,” said Brandi Felser, CEO, Sarcoma Foundation of America, in the press release. “With a current five-year survival rate as low as 36%, and for those with metastatic disease at diagnosis, as low as 20%, it is long past time that synovial sarcoma patients have expanded treatment options. Since one third of patients are diagnosed under age 30, improved outcomes can have a tremendous impact. Today, there is a renewed sense of hope for this patient community.”
In order for a patient to be treated with Tecelra, they must undergo biomarker tests for human leukocyte antigens type and melanoma-associated antigen A4 (MAGE-A4) tumor expression. As part of development, Adaptimmune partnered with Agilent Technologies for a companion diagnostic for the MAGE-A4 biomarker, MAGE-A4 IHC 1F9 pharmDx, which also received approval today from the FDA.1
“Tecelra (afami-cel), which uses each patient’s own immune cells to recognize and attack their cancer cells in a one-time infusion treatment, is significantly different than the current standards of care for advanced synovial sarcoma,” said Sandra D’Angelo, MD, sarcoma medical oncologist, cell therapist, Memorial Sloan Kettering Cancer Center, SPEARHEAD trial clinical investigator, in the press release. “This approval represents a much-needed new option for people diagnosed with this sarcoma and an important milestone for the use of cell therapies in solid tumor cancers.”