{"entity":{"id":"veritac-2","kind":"trial","name":"VERITAC-2","aka":[],"tldr":"The trial that got the first PROTAC approved, with benefit only in tumours with ESR1 mutations.","summary":"VERITAC-2, trial NCT05654623 sponsored by Arvinas and Pfizer and reported in 2025, is the trial that got the first PROTAC, vepdegestrant, approved, with benefit only in tumours carrying ESR1 mutations. It randomised 624 patients with ER-positive, HER2-negative advanced breast cancer after a CDK4/6 inhibitor and endocrine therapy to vepdegestrant or fulvestrant, met its primary progression-free survival endpoint in the ESR1-mutant population and not in the overall population, and led to approval in the second quarter of 2026 for ESR1-mutant disease. OnCo links it to HR-positive breast cancer, the oestrogen receptor as a target, vepdegestrant, fulvestrant and the first PROTAC paper, and it mirrors EMERALD with elacestrant, so two oral ER-degrading agents now show the same pattern. Whether degrading the receptor offers anything over the oral SERDs is the open question.","status":"mixed","asOf":"2026-09-04","links":[{"label":"ClinicalTrials.gov NCT05654623","url":"https://clinicaltrials.gov/study/NCT05654623"}],"tags":[],"related":[],"cancers":["breast-hr-positive"],"sections":[],"technologies":["endocrine-therapy","protac-degrader"],"targets":["estrogen-receptor"],"drugs":["vepdegestrant"],"companies":["arvinas"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-protac-concept-sakamoto-pnas-2001"],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT05654623","phase":"3","setting":"ER+/HER2- advanced breast cancer after CDK4/6 and endocrine therapy: vepdegestrant vs fulvestrant","sponsor":"Arvinas / Pfizer","result":"PFS HR 0.57 in ESR1-mutant; ITT not significant.","started":"2023-03-03","startedType":"actual","yearReported":2025,"enrolled":624,"enrolledBasis":"registry","outcomes":[{"endpoint":"Progression-free survival, ESR1-mutant (BICR)","primary":true,"unit":"months","arms":[{"name":"Vepdegestrant","n":136,"value":5},{"name":"Fulvestrant","n":134,"value":2.1}],"hr":0.57,"ci":[0.42,0.77],"p":"<0.001","source":"https://ascopubs.org/doi/10.1200/JCO.2025.43.17_suppl.LBA1000"},{"endpoint":"Progression-free survival, ITT","primary":true,"unit":"months","arms":[{"name":"Vepdegestrant","n":313,"value":3.7,"note":"Not significant"},{"name":"Fulvestrant","n":311,"value":3.6}],"hr":0.83,"ci":[0.68,1.02],"source":"https://ascopubs.org/doi/10.1200/JCO.2025.43.17_suppl.LBA1000"}],"replication":"Mirrors EMERALD (elacestrant): benefit confined to ESR1-mutant tumours. Two oral ER-degrading agents now show the same pattern."},"route":"/trials/veritac-2/","neighbours":{"cancer":[{"id":"breast-hr-positive","kind":"cancer","name":"HR-positive / HER2-negative breast cancer","route":"/cancers/breast-hr-positive/"}],"technology":[{"id":"endocrine-therapy","kind":"technology","name":"Endocrine therapy (SERMs, AIs, SERDs)","route":"/technologies/endocrine-therapy/"},{"id":"protac-degrader","kind":"technology","name":"PROTACs & molecular glues (targeted protein degradation)","route":"/technologies/protac-degrader/"}],"target":[{"id":"estrogen-receptor","kind":"target","name":"Estrogen receptor (ERα)","route":"/targets/estrogen-receptor/"}],"drug":[{"id":"fulvestrant","kind":"drug","name":"Fulvestrant","route":"/drugs/fulvestrant/"},{"id":"vepdegestrant","kind":"drug","name":"Vepdegestrant","route":"/drugs/vepdegestrant/"}],"company":[{"id":"arvinas","kind":"company","name":"Arvinas","route":"/companies/arvinas/"}],"paper":[{"id":"paper-protac-concept-sakamoto-pnas-2001","kind":"paper","name":"The first PROTAC: a chimeric molecule that tags a protein for destruction","route":"/key-papers/paper-protac-concept-sakamoto-pnas-2001/"}],"roadmap":[{"id":"hormonal-therapy-roadmap","kind":"roadmap","name":"Hormonal therapy roadmap: removing the ovaries → tamoxifen → oral degraders switched by a blood test","route":"/roadmaps/hormonal-therapy-roadmap/"},{"id":"targeted-therapy-roadmap","kind":"roadmap","name":"Targeted therapy roadmap: imatinib → designed for resistance → the undruggable drivers fall","route":"/roadmaps/targeted-therapy-roadmap/"}]}}