{"entity":{"id":"destiny-gastric04","kind":"trial","name":"DESTINY-Gastric04","aka":[],"tldr":"The first randomised proof that a HER2 drug beats standard chemotherapy in second-line stomach cancer: Enhertu added about three months of life.","summary":"DESTINY-Gastric04, trial NCT04704934 sponsored by Daiichi Sankyo and AstraZeneca and reported at the ASCO 2025 plenary and in the New England Journal of Medicine, was the first randomised proof that a HER2 drug beats standard chemotherapy in second-line HER2-positive gastric cancer, with trastuzumab deruxtecan adding a few months of life. It randomised 494 patients after trastuzumab to trastuzumab deruxtecan or ramucirumab plus paclitaxel and met its primary overall survival endpoint, also improving progression-free survival, confirming the accelerated approvals from DESTINY-Gastric01 and DESTINY-Gastric02; interstitial lung disease requires monitoring. Where it sits after zanidatamab-based first-line therapy is the open question.","status":"positive","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT04704934","url":"https://clinicaltrials.gov/study/NCT04704934"}],"tags":[],"related":[],"cancers":["gastric","gastric-her2-positive"],"sections":[],"technologies":["adc","topoisomerase-inhibitors"],"targets":["her2"],"drugs":["trastuzumab-deruxtecan","ramucirumab"],"companies":["daiichi-sankyo","astrazeneca"],"institutions":[],"pathways":[],"terms":["ild"],"trials":[],"people":["shitara-kohei"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT04704934","phase":"3","setting":"Second-line HER2-positive gastric/GEJ cancer after trastuzumab: T-DXd vs ramucirumab + paclitaxel","sponsor":"Daiichi Sankyo / AstraZeneca","result":"OS 14.7 vs 11.4 months, HR 0.70.","started":"2021-05-21","startedType":"actual","yearReported":2025,"enrolled":494,"enrolledBasis":"registry","outcomes":[{"endpoint":"Overall survival","primary":true,"unit":"months","arms":[{"name":"T-DXd 6.4 mg/kg","n":246,"value":14.7},{"name":"Ramucirumab + paclitaxel","n":248,"value":11.4}],"hr":0.7,"source":"https://www.asco.org/about-asco/press-center/news-releases/trastuzumab-deruxtecan-can-help-some-people-with-advanced-gastric-cancers-live-about-3-months-longer"}],"replication":"Consistent with DESTINY-Gastric01 (OS 12.5 vs 8.4 months vs chemotherapy, third line)."},"route":"/trials/destiny-gastric04/","neighbours":{"cancer":[{"id":"gastric","kind":"cancer","name":"Gastric & gastro-oesophageal junction cancer","route":"/cancers/gastric/"},{"id":"gastric-her2-positive","kind":"cancer","name":"HER2-positive gastric cancer","route":"/cancers/gastric-her2-positive/"},{"id":"esophageal","kind":"cancer","name":"Oesophageal cancer","route":"/cancers/esophageal/"}],"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":"her2","kind":"target","name":"HER2","route":"/targets/her2/"}],"drug":[{"id":"ramucirumab","kind":"drug","name":"Ramucirumab","route":"/drugs/ramucirumab/"},{"id":"trastuzumab-deruxtecan","kind":"drug","name":"Trastuzumab deruxtecan","route":"/drugs/trastuzumab-deruxtecan/"}],"company":[{"id":"astrazeneca","kind":"company","name":"AstraZeneca","route":"/companies/astrazeneca/"},{"id":"daiichi-sankyo","kind":"company","name":"Daiichi Sankyo","route":"/companies/daiichi-sankyo/"}],"term":[{"id":"ild","kind":"term","name":"Interstitial lung disease (ILD) / pneumonitis","route":"/terms/ild/"}],"person":[{"id":"shitara-kohei","kind":"person","name":"Kohei Shitara","route":"/people/shitara-kohei/"}],"pairing":[{"id":"her2-gastric-sequence","kind":"pairing","name":"HER2 sequence in gastric cancer: zanidatamab/trastuzumab + chemo ± PD-1 → T-DXd","route":"/pairings/her2-gastric-sequence/"}]}}