{"entity":{"id":"trastuzumab-duocarmazine","kind":"drug","name":"Trastuzumab duocarmazine","aka":[],"tldr":"A HER2 ADC with a DNA-alkylating payload that beat chemotherapy in a phase 3 trial yet never reached the market, because eye and lung toxicity and a stronger rival arrived first.","summary":"Byondis' duocarmycin-payload HER2 ADC improved PFS over physician's choice in pretreated HER2+ metastatic breast cancer (TULIP, 2021; PFS 7.0 vs 4.9 months) but with frequent ocular toxicity (~78%) and ILD. The FDA issued a complete response letter in 2023; the EMA application was withdrawn in 2024. Trastuzumab deruxtecan's DESTINY-Breast03 result made its niche disappear.\n\nLesson: statistical significance is not enough when a competitor redefines the standard; payload toxicity profile decides whether an ADC survives.","status":"withdrawn","asOf":"2026-09-06","links":[{"label":"TULIP (Ann Oncol 2021 abstract)","url":"https://www.annalsofoncology.org/article/S0923-7534(21)04434-8/fulltext"}],"tags":["failure","lesson:toxicity"],"related":[],"cancers":["breast-her2-positive"],"sections":[],"technologies":["adc"],"targets":["her2"],"drugs":["trastuzumab-deruxtecan"],"companies":["byondis"],"institutions":[],"pathways":[],"terms":[],"trials":["nct03262935","nct04205630","i-spy-2-2"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"code":"SYD985","modality":"ADC","payload":"seco-DUBA (duocarmycin)","linker":"Val-Cit cleavable","mechanism":"Trastuzumab with seco-DUBA duocarmycin via cleavable Val-Cit linker; DNA alkylation.","approvals":[],"mechanismSteps":[],"toxicity":[],"access":[],"regulatoryEvents":[]},"route":"/drugs/trastuzumab-duocarmazine/","neighbours":{"cancer":[{"id":"breast-her2-positive","kind":"cancer","name":"HER2-positive breast cancer","route":"/cancers/breast-her2-positive/"}],"technology":[{"id":"adc","kind":"technology","name":"Antibody-drug conjugate (ADC)","route":"/technologies/adc/"}],"target":[{"id":"her2","kind":"target","name":"HER2","route":"/targets/her2/"}],"drug":[{"id":"trastuzumab-deruxtecan","kind":"drug","name":"Trastuzumab deruxtecan","route":"/drugs/trastuzumab-deruxtecan/"}],"company":[{"id":"byondis","kind":"company","name":"Byondis","route":"/companies/byondis/"}],"trial":[{"id":"i-spy-2-2","kind":"trial","name":"I-SPY 2.2","route":"/trials/i-spy-2-2/"},{"id":"nct04205630","kind":"trial","name":"SYD985 in Patients With HER2-expressing Recurrent, Advanced or Metastatic Endometrial Carcinoma","route":"/trials/nct04205630/"},{"id":"nct03262935","kind":"trial","name":"SYD985 vs. Physician's Choice in Participants With HER2-positive Locally Advanced or Metastatic Breast Cancer","route":"/trials/nct03262935/"}],"bottleneck":[{"id":"b-negative-results","kind":"bottleneck","name":"Failures are hidden","route":"/bottlenecks/b-negative-results/"}]}}