{"entity":{"id":"idea-her2-adc-serous-endometrial","kind":"idea","name":"HER2 ADCs as standard for HER2-positive serous endometrial cancer","aka":[],"tldr":"Serous endometrial cancers often overproduce HER2. Enhertu already works in them; testing HER2 in every p53-abnormal tumour and using the ADC earlier could change outcomes for the worst subtype.","summary":"Serous endometrial carcinomas, which fall in the p53-abnormal molecular class, frequently amplify HER2, and this idea proposes testing HER2 in every p53-abnormal tumour and using trastuzumab deruxtecan earlier. T-DXd produced a high response rate in HER2 IHC 3+ endometrial cancer in DESTINY-PanTumor02, leading to tumour-agnostic approval, and trastuzumab with chemotherapy improved progression-free survival in a randomised phase 2 reported by Fader in 2018. The rationale is strong single-agent activity, a defined biomarker, and a subtype with the shortest survival that gains least from immunotherapy. The proposed test is a randomised phase 3 of first-line chemo-immunotherapy with or without T-DXd in HER2-positive p53abn disease, at an early clinical stage; NRG-GY026 tests trastuzumab.","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT04482309: DESTINY-PanTumor02","url":"https://clinicaltrials.gov/study/NCT04482309"}],"tags":[],"related":[],"cancers":["endometrial"],"sections":[],"technologies":[],"targets":["her2","tp53"],"drugs":["trastuzumab-deruxtecan","trastuzumab"],"companies":[],"institutions":[],"pathways":[],"terms":["endometrial-molecular-classes"],"trials":["destiny-pantumor02"],"people":[],"bottlenecks":[],"keyPapers":["paper-yarden-sliwkowski-erbb-network-nrmcb-2001"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Adding T-DXd (or trastuzumab) to first-line chemo-immunotherapy in HER2-positive p53abn endometrial cancer improves PFS and OS.","rationale":"Strong single-agent activity, a defined biomarker, and a subtype with the highest mortality and least benefit from immunotherapy.","test":"Randomised phase 3 of chemo-IO ± T-DXd (or sequential T-DXd) in HER2 IHC 2+/3+ p53abn disease; NRG-GY026 tests trastuzumab/pertuzumab with chemotherapy.","maturity":"early-clinical"},"route":"/ideas/idea-her2-adc-serous-endometrial/","neighbours":{"cancer":[{"id":"endometrial","kind":"cancer","name":"Endometrial cancer","route":"/cancers/endometrial/"},{"id":"endometrial-p53-abnormal","kind":"cancer","name":"p53-abnormal endometrial cancer, including uterine serous carcinoma","route":"/cancers/endometrial-p53-abnormal/"},{"id":"uterine-carcinosarcoma","kind":"cancer","name":"Uterine carcinosarcoma","route":"/cancers/uterine-carcinosarcoma/"}],"target":[{"id":"her2","kind":"target","name":"HER2","route":"/targets/her2/"},{"id":"tp53","kind":"target","name":"TP53","route":"/targets/tp53/"}],"drug":[{"id":"trastuzumab","kind":"drug","name":"Trastuzumab","route":"/drugs/trastuzumab/"},{"id":"trastuzumab-deruxtecan","kind":"drug","name":"Trastuzumab deruxtecan","route":"/drugs/trastuzumab-deruxtecan/"}],"term":[{"id":"endometrial-molecular-classes","kind":"term","name":"Endometrial cancer molecular classes (POLEmut, MMRd, p53abn, NSMP)","route":"/terms/endometrial-molecular-classes/"}],"trial":[{"id":"destiny-pantumor02","kind":"trial","name":"DESTINY-PanTumor02","route":"/trials/destiny-pantumor02/"}],"paper":[{"id":"paper-yarden-sliwkowski-erbb-network-nrmcb-2001","kind":"paper","name":"Yarden and Sliwkowski 2001: untangling the ErbB signalling network","route":"/key-papers/paper-yarden-sliwkowski-erbb-network-nrmcb-2001/"}]}}