{"entity":{"id":"brenetafusp","kind":"drug","name":"Brenetafusp","aka":[],"tldr":"Brenetafusp is a soluble T-cell receptor bispecific, tebentafusp's successor, that recognises a PRAME peptide on HLA-A*02:01 and drags T cells onto the tumour. A phase 3 with nivolumab in first-line melanoma is enrolling, but only patients carrying HLA-A*02:01, about half of those of European ancestry, are eligible.","summary":"Phase 1/2 in heavily pretreated cutaneous melanoma: median OS 14.3 months on monotherapy (ASCO 2026 update). PRISM-MEL-301 phase 3 with nivolumab in first-line HLA-A*02:01-positive melanoma is enrolling; further trials in ovarian, lung, and endometrial cancer. Requires HLA-A*02:01 (roughly half of European-ancestry patients).","status":"phase-3","asOf":"2026-09-07","links":[{"label":"Immunocore ASCO 2026 data","url":"https://www.globenewswire.com/news-release/2026/05/31/3303917/0/en/immunocore-presents-updated-phase-1-data-of-brenetafusp-in-patients-with-heavily-pretreated-advanced-melanoma.html"}],"tags":[],"related":[],"cancers":["melanoma","ovarian","nsclc"],"sections":[],"technologies":["t-cell-engager"],"targets":["prame","cd3","hla-a"],"drugs":["tebentafusp"],"companies":["immunocore"],"institutions":[],"pathways":[],"terms":[],"trials":["prism-mel-301","nct04262466"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"code":"IMC-F106C","modality":"ImmTAC (PRAME TCR × CD3 bispecific)","mechanism":"Affinity-enhanced TCR binding PRAME peptide-HLA-A*02:01 fused to an anti-CD3 scFv; redirects polyclonal T cells.","approvals":[],"mechanismSteps":["The TCR arm binds PRAME peptide displayed on HLA-A*02:01 on the tumour cell","The CD3 arm engages any nearby T cell","An artificial immune synapse forms and the T cell releases perforin and granzymes","Interferon-gamma release upregulates PD-L1, the rationale for pairing with nivolumab"],"dosing":{"route":"Intravenous","schedule":"Weekly with step-up dosing to 160 µg","monitoring":"Cytokine release syndrome during the first doses; rash","source":"https://clinicaltrials.gov/study/NCT06112314"},"toxicity":[],"access":[],"regulatoryEvents":[{"date":"2024","type":"designation","region":"US","note":"Phase 3 PRISM-MEL-301 initiated after FDA alignment on design"}]},"route":"/drugs/brenetafusp/","neighbours":{"cancer":[{"id":"advanced-melanoma","kind":"cancer","name":"Advanced melanoma (unresectable stage III and stage IV)","route":"/cancers/advanced-melanoma/"},{"id":"melanoma","kind":"cancer","name":"Melanoma","route":"/cancers/melanoma/"},{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"},{"id":"ovarian","kind":"cancer","name":"Ovarian cancer","route":"/cancers/ovarian/"},{"id":"uveal-melanoma","kind":"cancer","name":"Uveal melanoma","route":"/cancers/uveal-melanoma/"}],"technology":[{"id":"t-cell-engager","kind":"technology","name":"T-cell engagers (bispecific)","route":"/technologies/t-cell-engager/"}],"target":[{"id":"cd3","kind":"target","name":"CD3","route":"/targets/cd3/"},{"id":"hla-a","kind":"target","name":"HLA-A","route":"/targets/hla-a/"},{"id":"prame","kind":"target","name":"PRAME","route":"/targets/prame/"}],"drug":[{"id":"tebentafusp","kind":"drug","name":"Tebentafusp","route":"/drugs/tebentafusp/"}],"company":[{"id":"immunocore","kind":"company","name":"Immunocore","route":"/companies/immunocore/"}],"trial":[{"id":"prism-mel-301","kind":"trial","name":"PRISM-MEL-301","route":"/trials/prism-mel-301/"},{"id":"nct04262466","kind":"trial","name":"Safety and Efficacy of IMC-F106C as a Single Agent and in Combination With Checkpoint Inhibitors","route":"/trials/nct04262466/"}],"term":[{"id":"hla-a02-restriction","kind":"term","name":"HLA-A*02:01 restriction","route":"/terms/hla-a02-restriction/"},{"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/"}],"idea":[{"id":"idea-prame-tcr-beyond-a02","kind":"idea","name":"TCR therapeutics for non-HLA-A*02 patients","route":"/ideas/idea-prame-tcr-beyond-a02/"}]}}