{"entity":{"id":"ascent-04","kind":"trial","name":"ASCENT-04 / KEYNOTE-D19","aka":[],"tldr":"Showed that pairing an ADC with immunotherapy beats chemotherapy plus immunotherapy in first-line PD-L1-positive TNBC.","summary":"ASCENT-04, also KEYNOTE-D19, trial NCT05382286 sponsored by Gilead and Merck and reported at ESMO 2025, showed that pairing the antibody-drug conjugate sacituzumab govitecan with pembrolizumab beats chemotherapy plus pembrolizumab in first-line PD-L1-positive metastatic triple-negative breast cancer. It randomised 443 patients with a combined positive score of ten or more, met its primary progression-free survival endpoint by blinded review, showed improved time to second progression at ASCO 2026 with overall survival immature, and was approved in 2026, establishing ADC plus checkpoint inhibitor as the new first-line standard for PD-L1-positive disease. OnCo links it to triple-negative breast cancer, sacituzumab govitecan, pembrolizumab, the ADC plus checkpoint inhibitor pairing and four roadmaps. Whether the survival benefit follows is the open question.","status":"positive","asOf":"2026-09-04","links":[{"label":"ClinicalTrials.gov NCT05382286","url":"https://clinicaltrials.gov/study/NCT05382286"},{"label":"ASCENT-04/KEYNOTE-D19 (NEJM 2026)","url":"https://doi.org/10.1056/NEJMoa2508959"}],"tags":[],"related":[],"cancers":["tnbc","tnbc-metastatic"],"sections":[],"technologies":["adc","topoisomerase-inhibitors"],"targets":[],"drugs":["sacituzumab-govitecan","pembrolizumab"],"companies":["gilead","merck"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-ascent-04-n-engl-j-med-2026"],"journals":[],"dependsOn":[],"notes":["Primary paper (NEJM 2026): 443 patients with CPS 10 or more randomised 1 to 1 to sacituzumab govitecan with pembrolizumab or chemotherapy with pembrolizumab; progression-free survival 11.2 versus 7.8 months (hazard ratio 0.65), response 60 versus 53 percent, duration of response 16.5 versus 9.2 months, discontinuation for adverse events 12 versus 31 percent, deaths from adverse events 3 percent in each arm; overall survival immature. UK sites (registry, 8): NHS Lothian, Beatson Glasgow, Leeds, Barts, Royal Free, Guy's and St Thomas', University College London Hospitals, Nottingham. No NICE appraisal listed on 24 September 2026."],"nct":"NCT05382286","phase":"3","setting":"First-line PD-L1+ (CPS ≥10) metastatic TNBC: sacituzumab govitecan + pembrolizumab vs chemotherapy + pembrolizumab","sponsor":"Gilead / Merck","result":"PFS HR 0.65; PFS2 improved.","started":"2022-07-25","startedType":"actual","yearReported":2025,"enrolled":443,"enrolledBasis":"registry","outcomes":[{"endpoint":"Progression-free survival (BICR)","primary":true,"unit":"months","arms":[{"name":"Sacituzumab govitecan + pembrolizumab","n":221,"value":11.2},{"name":"Chemotherapy + pembrolizumab","n":222,"value":7.8}],"hr":0.65,"ci":[0.51,0.84],"p":"0.0009","source":"https://dailyreporter.esmo.org/esmo-congress-2025/breast-cancer/survival-improvements-observed-with-first-line-antibody-drug-conjugates-in-triple-negative-breast-cancer"},{"endpoint":"Objective response rate","unit":"%","arms":[{"name":"Sacituzumab govitecan + pembrolizumab","value":60},{"name":"Chemotherapy + pembrolizumab","value":53}],"source":"https://doi.org/10.1056/NEJMoa2508959"},{"endpoint":"Overall survival","unit":"months","arms":[{"name":"Sacituzumab govitecan + pembrolizumab","note":"Immature; PFS2 favoured the ADC arm in the ASCO 2026 update."},{"name":"Chemotherapy + pembrolizumab"}],"source":"https://doi.org/10.1056/NEJMoa2508959"}],"replication":"First trial of ADC + PD-1 in TNBC; the design mirrors EV-302 in urothelial cancer. TROPION-Breast05 (Dato-DXd + durvalumab) will be the confirmatory sibling."},"route":"/trials/ascent-04/","neighbours":{"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/"}],"drug":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"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/"},{"id":"merck","kind":"company","name":"Merck & Co. (MSD)","route":"/companies/merck/"}],"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-nccn-breast-cancer-v4-2026-jnccn-2026","kind":"paper","name":"Breast Cancer, Version 4.2026, NCCN Clinical Practice Guidelines In Oncology","route":"/key-papers/paper-nccn-breast-cancer-v4-2026-jnccn-2026/"},{"id":"paper-ascent-04-n-engl-j-med-2026","kind":"paper","name":"Sacituzumab Govitecan plus Pembrolizumab for Advanced Triple-Negative Breast Cancer","route":"/key-papers/paper-ascent-04-n-engl-j-med-2026/"}],"roadmap":[{"id":"adc-generations","kind":"roadmap","name":"ADC roadmap: from Mylotarg to bispecific and dual-payload ADCs","route":"/roadmaps/adc-generations/"},{"id":"immunotherapy-roadmap","kind":"roadmap","name":"Immunotherapy roadmap: Coley's toxins → checkpoint inhibitors → engineered immunity","route":"/roadmaps/immunotherapy-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-brain-metastasis-trials","kind":"idea","name":"Trials that include, and report, brain metastases in triple-negative breast cancer","route":"/ideas/idea-tnbc-brain-metastasis-trials/"},{"id":"idea-trop2-pet-selection","kind":"idea","name":"TROP2 PET to choose and sequence TROP2 ADCs","route":"/ideas/idea-trop2-pet-selection/"}],"term":[{"id":"tnbc-trials-open-today","kind":"term","name":"Triple-negative breast cancer trials open today (registry snapshot and UK sites)","route":"/terms/tnbc-trials-open-today/"}],"trial":[{"id":"ascent","kind":"trial","name":"ASCENT","route":"/trials/ascent/"},{"id":"keynote-355","kind":"trial","name":"KEYNOTE-355","route":"/trials/keynote-355/"}],"pairing":[{"id":"adc-plus-io","kind":"pairing","name":"ADC + checkpoint inhibitor","route":"/pairings/adc-plus-io/"}]}}