{"entity":{"id":"tebentafusp","kind":"drug","name":"Tebentafusp","aka":[],"tldr":"The first drug to improve survival in metastatic uveal melanoma, and the first TCR-based bispecific.","summary":"Tebentafusp is an ImmTAC: a soluble, affinity-enhanced T-cell receptor that recognises a gp100 peptide presented on HLA-A*02:01, fused to an anti-CD3 single-chain antibody that recruits any T cell to the melanoma cell. Because gp100 is a melanocyte-lineage protein, the drug also hits skin melanocytes, so rash and pruritus are expected. It is given weekly after step-up doses of 20, 30 and 68 micrograms, with inpatient monitoring for the first three doses because of cytokine release syndrome and hypotension. Approved in 2022 in the US and EU for HLA-A*02:01-positive metastatic uveal melanoma, it was the first drug to improve survival in that disease (overall survival 21.7 versus 16.0 months) and the first TCR-based bispecific approved anywhere. It is being tested in cutaneous melanoma after PD-1 therapy (TEBE-AM), and Immunocore's PRAME-directed brenetafusp follows the same design.","status":"approved","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Tebentafusp","links":[{"label":"FDA label (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/search.cfm?query=Tebentafusp"}],"tags":[],"related":["hla-a-02-01"],"cancers":["melanoma"],"sections":[],"technologies":["t-cell-engager","tcr-t"],"targets":["gp100","cd3","hla-a"],"drugs":[],"companies":["immunocore"],"institutions":[],"pathways":[],"terms":["step-up-dosing"],"trials":["nct05549297","nct04262466"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"brand":"Kimmtrak","modality":"ImmTAC (TCR×CD3 bispecific)","mechanism":"Soluble affinity-enhanced TCR against gp100 peptide-HLA fused to anti-CD3 scFv.","approvals":[{"region":"US","year":2022,"indication":"HLA-A*02:01+ metastatic uveal melanoma"}],"mechanismSteps":["Soluble high-affinity TCR binds gp100 peptide presented on HLA-A*02:01 on melanoma cells","Fused anti-CD3 scFv recruits any T cell","Immune synapse forms; T cell releases cytotoxic granules","Melanocytic tumour cells are killed; skin melanocytes cause rash","Weekly redosing maintains pressure"],"dosing":{"route":"IV infusion","schedule":"20 µg day 1, 30 µg day 8, 68 µg day 15, then 68 µg weekly","modifications":"Hold for grade ≥3 CRS; skin reactions managed with antihistamines and steroids","monitoring":"Inpatient monitoring for first three doses; blood pressure, temperature, LFTs","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications"},"toxicity":[{"event":"Cytokine release syndrome"},{"event":"Rash"},{"event":"Pyrexia"},{"event":"Pruritus"},{"event":"Fatigue"},{"event":"Nausea"},{"event":"Hypotension"},{"event":"Transaminase increase"}],"access":[{"country":"US","reimbursement":"Medicare Part B (physician-administered); commercial plans per formulary","assistance":"https://www.kimmtrak.com","source":"https://www.cms.gov/medicare/payment/part-b-drugs/asp-pricing-files","asOf":"2026-09-06"},{"country":"UK","reimbursement":"NICE: recommended for HLA-A*02:01+ metastatic uveal melanoma (TA867)","source":"https://www.nice.org.uk/guidance/published?ngt=Technology%20appraisal%20guidance","asOf":"2026-09-06"}],"regulatoryEvents":[{"date":"2021-02","type":"designation","region":"US","note":"Breakthrough Therapy designation","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications"},{"date":"2022-01-25","type":"approval","region":"US","note":"HLA-A*02:01+ unresectable or metastatic uveal melanoma: first TCR therapeutic approved","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications"},{"date":"2022-04","type":"approval","region":"EU","note":"EMA approval","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications"}]},"route":"/drugs/tebentafusp/","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":"melanoma","kind":"cancer","name":"Melanoma","route":"/cancers/melanoma/"},{"id":"uveal-melanoma","kind":"cancer","name":"Uveal melanoma","route":"/cancers/uveal-melanoma/"}],"technology":[{"id":"percutaneous-hepatic-perfusion","kind":"technology","name":"Percutaneous hepatic perfusion (chemosaturation)","route":"/technologies/percutaneous-hepatic-perfusion/"},{"id":"t-cell-engager","kind":"technology","name":"T-cell engagers (bispecific)","route":"/technologies/t-cell-engager/"},{"id":"tcr-t","kind":"technology","name":"TCR-T cell therapy","route":"/technologies/tcr-t/"}],"target":[{"id":"cd3","kind":"target","name":"CD3","route":"/targets/cd3/"},{"id":"gp100","kind":"target","name":"gp100 (PMEL)","route":"/targets/gp100/"},{"id":"hla-a","kind":"target","name":"HLA-A","route":"/targets/hla-a/"}],"company":[{"id":"immunocore","kind":"company","name":"Immunocore","route":"/companies/immunocore/"}],"term":[{"id":"hla-a02-restriction","kind":"term","name":"HLA-A*02:01 restriction","route":"/terms/hla-a02-restriction/"},{"id":"step-up-dosing","kind":"term","name":"Step-up dosing (T-cell engagers)","route":"/terms/step-up-dosing/"},{"id":"uveal-melanoma-prognostic-markers","kind":"term","name":"Uveal melanoma prognostic markers (GNAQ/GNA11, monosomy 3, gene-expression class)","route":"/terms/uveal-melanoma-prognostic-markers/"}],"trial":[{"id":"imcgp100-202","kind":"trial","name":"IMCgp100-202","route":"/trials/imcgp100-202/"},{"id":"nct04262466","kind":"trial","name":"Safety and Efficacy of IMC-F106C as a Single Agent and in Combination With Checkpoint Inhibitors","route":"/trials/nct04262466/"},{"id":"nct05549297","kind":"trial","name":"Tebentafusp Regimen Versus Investigator's Choice in Previously Treated Advanced Melanoma (TEBE-AM)","route":"/trials/nct05549297/"}],"drug":[{"id":"brenetafusp","kind":"drug","name":"Brenetafusp","route":"/drugs/brenetafusp/"}],"idea":[{"id":"idea-bio1-pmhc-bispecifics-public-drivers","kind":"idea","name":"Antibodies that see mutant KRAS and p53 fragments displayed on the cell surface","route":"/ideas/idea-bio1-pmhc-bispecifics-public-drivers/"},{"id":"idea-prame-tcr-beyond-a02","kind":"idea","name":"TCR therapeutics for non-HLA-A*02 patients","route":"/ideas/idea-prame-tcr-beyond-a02/"}],"person":[{"id":"paul-nathan","kind":"person","name":"Paul Nathan","route":"/people/paul-nathan/"},{"id":"richard-carvajal","kind":"person","name":"Richard D. Carvajal","route":"/people/richard-carvajal/"}],"institution":[{"id":"oxford-cancer","kind":"institution","name":"Oxford Cancer (Oxford University Hospitals and University of Oxford)","route":"/institutions/oxford-cancer/"}]}}