{"entity":{"id":"ascent","kind":"trial","name":"ASCENT","aka":[],"tldr":"The trial that proved a TROP2 ADC could nearly double survival in heavily pretreated triple-negative breast cancer.","summary":"ASCENT, trial NCT02574455 sponsored by Gilead through Immunomedics and published in the New England Journal of Medicine in 2020, proved that the TROP2 antibody-drug conjugate sacituzumab govitecan could nearly double survival in heavily pretreated metastatic triple-negative breast cancer. It randomised 529 patients with at least two prior lines to sacituzumab govitecan or chemotherapy, met its primary progression-free survival endpoint in patients without brain metastases and showed a large overall survival benefit with a much higher response rate, regardless of TROP2 expression level, which shaped the view that immunohistochemistry selection is unnecessary for TROP2 ADCs. Whether TROP2 ADCs work equally well after other topoisomerase payloads is the open question.","status":"positive","asOf":"2026-09-04","links":[{"label":"ClinicalTrials.gov NCT02574455","url":"https://clinicaltrials.gov/study/NCT02574455"},{"label":"ASCENT primary analysis (NEJM 2021)","url":"https://doi.org/10.1056/NEJMoa2028485"},{"label":"ASCENT subgroup analyses (npj Breast Cancer 2024)","url":"https://doi.org/10.1038/s41523-024-00635-5"},{"label":"NICE TA819 (17 August 2022)","url":"https://www.nice.org.uk/guidance/ta819"}],"tags":[],"related":[],"cancers":["tnbc","tnbc-metastatic"],"sections":[],"technologies":["adc","topoisomerase-inhibitors"],"targets":["trop2"],"drugs":["sacituzumab-govitecan"],"companies":["gilead"],"institutions":[],"pathways":[],"terms":[],"trials":["ascent-03","ascent-04","keynote-119"],"people":["aditya-bardia"],"bottlenecks":[],"keyPapers":["paper-bardia-ascent-trop2-biomarker-ann-oncol-2021","paper-ascent-nejm-2021"],"journals":[],"dependsOn":[],"notes":["Design (NEJM 2021): 529 patients with relapsed or refractory metastatic triple-negative disease after at least two prior therapies randomised 1 to 1 to sacituzumab govitecan 10 mg/kg on days 1 and 8 of 21 or physician's choice of eribulin, vinorelbine, capecitabine or gemcitabine; 468 without brain metastases formed the primary population. Progression-free survival 5.6 versus 1.7 months (hazard ratio 0.41), overall survival 12.1 versus 6.7 months (0.48), response 35 versus 5 percent; grade 3 or higher neutropenia 51 versus 33 percent, diarrhoea 10 versus below 1 percent. Post hoc subgroups (npj Breast Cancer 2024): benefit held in patients aged 65 or over and in Black patients; among the 12 percent with stable brain metastases progression-free survival was numerically longer but overall survival similar.","UK sites (registry, 11): Colchester, University Hospital Coventry, University Hospital of North Durham, Royal Surrey Guildford, Hereford County Hospital, Royal Free London, the Christie, Nottingham City Hospital, Derriford Plymouth, Musgrove Park Taunton, Pinderfields Wakefield. NICE TA819 (17 August 2022) commissions the drug after two or more therapies."],"nct":"NCT02574455","phase":"3","setting":"Pretreated metastatic TNBC: sacituzumab govitecan vs chemotherapy","sponsor":"Gilead (Immunomedics)","result":"OS 12.1 vs 6.7 months, HR 0.48.","started":"2017-11-07","startedType":"actual","yearReported":2020,"enrolled":529,"enrolledBasis":"registry","outcomes":[{"endpoint":"Progression-free survival (patients without brain metastases)","primary":true,"unit":"months","arms":[{"name":"Sacituzumab govitecan","n":235,"value":5.6},{"name":"Chemotherapy (TPC)","n":233,"value":1.7}],"hr":0.41,"ci":[0.32,0.52],"p":"<0.001","source":"https://www.nejm.org/doi/full/10.1056/NEJMoa2028485"},{"endpoint":"Overall survival","unit":"months","arms":[{"name":"Sacituzumab govitecan","value":12.1},{"name":"Chemotherapy (TPC)","value":6.7}],"hr":0.48,"ci":[0.38,0.59],"p":"<0.001","source":"https://www.nejm.org/doi/full/10.1056/NEJMoa2028485"},{"endpoint":"Objective response rate","unit":"%","arms":[{"name":"Sacituzumab govitecan","value":35},{"name":"Chemotherapy (TPC)","value":5}],"source":"https://www.nejm.org/doi/full/10.1056/NEJMoa2028485"}],"replication":"Consistent with the single-arm IMMU-132-01 basket (ORR 33%) that led to accelerated approval, with TROPiCS-02 in HR+ disease, and with the first-line ASCENT-03/04 results; real-world series report similar PFS."},"route":"/trials/ascent/","neighbours":{"cancer":[{"id":"her2-low-metastatic-breast-cancer","kind":"cancer","name":"HER2-low and HER2-ultralow metastatic breast cancer","route":"/cancers/her2-low-metastatic-breast-cancer/"},{"id":"tnbc-metastatic","kind":"cancer","name":"Metastatic triple-negative breast cancer","route":"/cancers/tnbc-metastatic/"},{"id":"tnbc","kind":"cancer","name":"Triple-negative breast cancer (TNBC)","route":"/cancers/tnbc/"}],"technology":[{"id":"adc","kind":"technology","name":"Antibody-drug conjugate (ADC)","route":"/technologies/adc/"},{"id":"topoisomerase-inhibitors","kind":"technology","name":"Topoisomerase-I inhibitors (and ADC payloads)","route":"/technologies/topoisomerase-inhibitors/"}],"target":[{"id":"trop2","kind":"target","name":"TROP2","route":"/targets/trop2/"}],"drug":[{"id":"eribulin","kind":"drug","name":"Eribulin","route":"/drugs/eribulin/"},{"id":"sacituzumab-govitecan","kind":"drug","name":"Sacituzumab govitecan","route":"/drugs/sacituzumab-govitecan/"}],"company":[{"id":"gilead","kind":"company","name":"Gilead Sciences (incl. Kite)","route":"/companies/gilead/"}],"trial":[{"id":"ascent-03","kind":"trial","name":"ASCENT-03","route":"/trials/ascent-03/"},{"id":"ascent-04","kind":"trial","name":"ASCENT-04 / KEYNOTE-D19","route":"/trials/ascent-04/"},{"id":"keynote-119","kind":"trial","name":"KEYNOTE-119","route":"/trials/keynote-119/"}],"person":[{"id":"aditya-bardia","kind":"person","name":"Aditya Bardia","route":"/people/aditya-bardia/"}],"paper":[{"id":"paper-ascent-nejm-2021","kind":"paper","name":"ASCENT: sacituzumab govitecan doubles survival in heavily pretreated metastatic triple-negative breast cancer","route":"/key-papers/paper-ascent-nejm-2021/"},{"id":"paper-bardia-ascent-trop2-biomarker-ann-oncol-2021","kind":"paper","name":"Biomarker analyses in the phase III ASCENT study of sacituzumab govitecan versus chemotherapy in patients with metastatic triple-negative breast cancer","route":"/key-papers/paper-bardia-ascent-trop2-biomarker-ann-oncol-2021/"},{"id":"paper-esmo-metastatic-breast-cancer-guideline-ann-oncol-2021","kind":"paper","name":"ESMO Clinical Practice Guideline for the diagnosis, staging and treatment of patients with metastatic breast cancer","route":"/key-papers/paper-esmo-metastatic-breast-cancer-guideline-ann-oncol-2021/"}],"term":[{"id":"her2-low-and-trop2-adc-eligibility-tnbc","kind":"term","name":"HER2-low eligibility for trastuzumab deruxtecan, and TROP2 ADCs without a test (triple-negative disease)","route":"/terms/her2-low-and-trop2-adc-eligibility-tnbc/"},{"id":"tnbc-symptom-control-palliation","kind":"term","name":"Palliation in advanced triple-negative breast cancer: brain, bone, pleura, skin and end of life","route":"/terms/tnbc-symptom-control-palliation/"}],"roadmap":[{"id":"tnbc-history","kind":"roadmap","name":"TNBC roadmap: from 'nothing to target' to ADC + immunotherapy first line","route":"/roadmaps/tnbc-history/"},{"id":"tnbc-roadmap","kind":"roadmap","name":"Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem","route":"/roadmaps/tnbc-roadmap/"},{"id":"trop2-adc-roadmap","kind":"roadmap","name":"TROP2 ADC roadmap: sacituzumab govitecan → Dato-DXd → sac-TMT → bispecifics and PET","route":"/roadmaps/trop2-adc-roadmap/"}],"idea":[{"id":"idea-tnbc-adc-sequencing-trial","kind":"idea","name":"A randomised trial of antibody-drug conjugate sequence in metastatic triple-negative breast cancer","route":"/ideas/idea-tnbc-adc-sequencing-trial/"},{"id":"idea-trop2-pet-selection","kind":"idea","name":"TROP2 PET to choose and sequence TROP2 ADCs","route":"/ideas/idea-trop2-pet-selection/"}]}}