{"entity":{"id":"afamitresgene-autoleucel","kind":"drug","name":"Afamitresgene autoleucel","aka":[],"tldr":"Afamitresgene autoleucel was the first engineered T-cell receptor therapy approved for a solid tumour, synovial sarcoma.","summary":"Afamitresgene autoleucel (afami-cel) is a TCR-T therapy: patient T cells are engineered with an affinity-enhanced T-cell receptor that recognises the MAGE-A4 230-239 peptide on HLA-A*02, so eligibility requires both HLA typing and tumour MAGE-A4 testing. It received accelerated approval in August 2024 for advanced MAGE-A4-positive, HLA-A*02-positive synovial sarcoma on SPEARHEAD-1 (ORR about 39%, median duration of response about 12 months), and in Q2 2026 the label was extended to patients aged 12 and over. Treatment is a single infusion of 2.68 to 10 x 10^9 TCR-positive cells after fludarabine and cyclophosphamide; cytokine release syndrome and prolonged cytopenias are the main risks. Whether responses are durable enough to change survival is open. For a newcomer: the first engineered T-cell receptor therapy approved for a solid tumour.","status":"approved","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Afamitresgene_autoleucel","links":[{"label":"FDA label (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/search.cfm?query=Afamitresgene%20autoleucel"}],"tags":[],"related":["hla-a-02-01"],"cancers":["sarcoma","synovial-sarcoma"],"sections":[],"technologies":["tcr-t"],"targets":["mage-a4","hla-a"],"drugs":[],"companies":["adaptimmune"],"institutions":[],"pathways":[],"terms":[],"trials":["nct05642455","nct04044768"],"people":[],"bottlenecks":[],"keyPapers":["paper-spearhead-1-lancet-2024"],"journals":[],"dependsOn":[],"notes":[],"brand":"Tecelra","code":"afami-cel","modality":"TCR-T (MAGE-A4)","mechanism":"Affinity-enhanced TCR against MAGE-A4 230-239/HLA-A*02.","approvals":[{"region":"US","year":2024,"indication":"Advanced MAGE-A4+ synovial sarcoma, HLA-A*02+ (age ≥12 from 2026)"}],"mechanismSteps":["Patient's T cells are engineered to express an affinity-enhanced TCR recognising MAGE-A4 peptide on HLA-A*02","Cells are expanded and infused after lymphodepletion","TCR-T cells recognise MAGE-A4-derived peptide displayed by tumour cells","Cytotoxic granules kill the tumour cell","Persistence provides ongoing surveillance"],"dosing":{"route":"Single IV infusion after lymphodepletion","schedule":"2.68 × 10⁹ to 10 × 10⁹ MAGE-A4 TCR+ T cells; fludarabine 30 mg/m² ×4 and cyclophosphamide 600 mg/m² ×3","modifications":"Tocilizumab/steroids for CRS","monitoring":"Daily monitoring for 7 days; cytopenias; infections","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications"},"toxicity":[{"event":"Cytokine release syndrome"},{"event":"Nausea"},{"event":"Vomiting"},{"event":"Fatigue"},{"event":"Infections"},{"event":"Prolonged cytopenias"}],"access":[{"country":"US","listPrice":"$727,000 per infusion (list price at launch, 2024)","reimbursement":"Medicare Part B (inpatient/outpatient); commercial per plan","asOf":"2026-09-06"}],"regulatoryEvents":[{"date":"2024-08-01","type":"approval","region":"US","note":"Accelerated approval, MAGE-A4+ HLA-A*02+ advanced synovial sarcoma (SPEARHEAD-1): first TCR-T for a solid tumour","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications"},{"date":"2024-08-02","type":"accelerated-approval","region":"US","note":"Accelerated approval on a surrogate endpoint; the confirmatory requirement was still open 2.1 years later, when the FDA's table was read.","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-afamitresgene-autoleucel-unresectable-or-metastatic-synovial-sarcoma","indication":"Treatment of adults with unresectable or metastatic synovial sarcoma who have received prior chemotherapy, are HLA-A*02:01P, -A*02:02P, -A*02:03P, or -A*02:06P positive and whose tumor expresses the MAGE-A4 antigen as determined by FDA-approved or cleared companion diagnostic devices."},{"date":"2025-08","type":"filing","region":"US","note":"US rights sold by Adaptimmune to US WorldMeds","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications"},{"date":"2026-Q2","type":"label-change","region":"US","note":"Label extended to patients aged 12 and older","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications"}]},"route":"/drugs/afamitresgene-autoleucel/","neighbours":{"biomarker":[{"id":"hla-a-02-01","kind":"biomarker","name":"HLA-A*02:01 (HLA typing for TCR therapies)","route":"/biomarkers/hla-a-02-01/"}],"cancer":[{"id":"sarcoma","kind":"cancer","name":"Sarcomas (soft tissue, bone, GIST)","route":"/cancers/sarcoma/"},{"id":"synovial-sarcoma","kind":"cancer","name":"Synovial sarcoma","route":"/cancers/synovial-sarcoma/"}],"technology":[{"id":"tcr-t","kind":"technology","name":"TCR-T cell therapy","route":"/technologies/tcr-t/"}],"target":[{"id":"hla-a","kind":"target","name":"HLA-A","route":"/targets/hla-a/"},{"id":"mage-a4","kind":"target","name":"MAGE-A4","route":"/targets/mage-a4/"}],"company":[{"id":"adaptimmune","kind":"company","name":"Adaptimmune","route":"/companies/adaptimmune/"},{"id":"us-worldmeds","kind":"company","name":"US WorldMeds","route":"/companies/us-worldmeds/"}],"trial":[{"id":"nct04044768","kind":"trial","name":"Spearhead 1 Study in Subjects With Advanced Synovial Sarcoma or Myxoid/Round Cell Liposarcoma","route":"/trials/nct04044768/"},{"id":"nct05642455","kind":"trial","name":"SPEARHEAD-3 Pediatric Study","route":"/trials/nct05642455/"}],"paper":[{"id":"paper-spearhead-1-lancet-2024","kind":"paper","name":"SPEARHEAD-1: afamitresgene autoleucel, the first engineered T-cell receptor therapy approved for a solid tumour, in synovial sarcoma","route":"/key-papers/paper-spearhead-1-lancet-2024/"}],"term":[{"id":"hla-a02-restriction","kind":"term","name":"HLA-A*02:01 restriction","route":"/terms/hla-a02-restriction/"},{"id":"ss18-ssx-fusion","kind":"term","name":"SS18::SSX fusion (synovial sarcoma)","route":"/terms/ss18-ssx-fusion/"}],"idea":[{"id":"idea-tcr-t-beyond-hla-a2","kind":"idea","name":"Extending sarcoma TCR-T beyond HLA-A*02","route":"/ideas/idea-tcr-t-beyond-hla-a2/"}],"roadmap":[{"id":"cell-therapy-roadmap","kind":"roadmap","name":"Cell therapy roadmap: CD19 CAR-T → solid tumours → in vivo CAR","route":"/roadmaps/cell-therapy-roadmap/"}],"person":[{"id":"sandra-dangelo","kind":"person","name":"Sandra P. D'Angelo","route":"/people/sandra-dangelo/"}],"institution":[{"id":"ccc-tuebingen","kind":"institution","name":"Comprehensive Cancer Center Tübingen-Stuttgart","route":"/institutions/ccc-tuebingen/"}]}}