{"entity":{"id":"zanidatamab-zovodotin","kind":"drug","name":"Zanidatamab zovodotin","aka":["ZW49"],"tldr":"Zanidatamab zovodotin joined the two-armed HER2 antibody zanidatamab to a cell-killing payload. It was tested in early trials in HER2-expressing cancers; the plain antibody went on to approval, the conjugate did not progress beyond phase 1.","summary":"Zanidatamab zovodotin (ZW49) was Zymeworks' antibody-drug conjugate built on zanidatamab, the biparatopic HER2 antibody now approved as Ziihera. Binding two HER2 epitopes was intended to make the receptor cluster and internalise faster, delivering more of the auristatin payload into HER2-expressing tumour cells, including those with lower HER2 expression.\n\nIt was given intravenously in a phase 1 dose-escalation study across HER2-expressing solid tumours, including breast and gastro-oesophageal cancers. The programme was not advanced into registrational trials; it is named on the HER2-positive breast cancer page as one of the next-generation and biparatopic HER2 conjugates that followed trastuzumab deruxtecan.","status":"phase-1","asOf":"2026-09-17","links":[{"label":"Zimmerman and Esteva, Cancers 2024: next-generation HER2-targeted antibody-drug conjugates (table of payloads and linkers)","url":"https://doi.org/10.3390/cancers16040800"},{"label":"ClinicalTrials.gov NCT03821233 (phase 1)","url":"https://clinicaltrials.gov/study/NCT03821233"}],"tags":["subtype-drugs-wave"],"related":["zanidatamab","trastuzumab-deruxtecan"],"cancers":["breast-her2-positive","gastric","gallbladder"],"sections":[],"technologies":["adc"],"targets":["her2"],"drugs":[],"companies":["zymeworks"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Payload and linker read from the ADC table in Zimmerman and Esteva, Cancers 2024 (zovodotin, cleavable vc linker, DAR 2 to 4 variable); Niquille et al., MAbs 2024, describe the payload as a cytotoxic tubulin inhibitor delivered by the biparatopic antibody. Listed on the gallbladder page as the conjugate built on zanidatamab; the phase 1 study (NCT03821233) enrolled HER2-expressing solid tumours and the programme did not advance."],"code":"ZW49","modality":"Biparatopic HER2 antibody-drug conjugate","payload":"Zovodotin (auristatin-class tubulin inhibitor), variable DAR (2 to 4)","linker":"Cleavable valine-citrulline (vc) linker","mechanism":"The biparatopic antibody zanidatamab, which binds two different HER2 domains at once, carried an auristatin payload; the dual binding clusters HER2 and drives the conjugate into the cell where the payload is released.","approvals":[],"mechanismSteps":[],"toxicity":[],"access":[],"regulatoryEvents":[]},"route":"/drugs/zanidatamab-zovodotin/","neighbours":{"drug":[{"id":"trastuzumab-deruxtecan","kind":"drug","name":"Trastuzumab deruxtecan","route":"/drugs/trastuzumab-deruxtecan/"},{"id":"zanidatamab","kind":"drug","name":"Zanidatamab","route":"/drugs/zanidatamab/"}],"cancer":[{"id":"gallbladder","kind":"cancer","name":"Gallbladder cancer","route":"/cancers/gallbladder/"},{"id":"gastric","kind":"cancer","name":"Gastric & gastro-oesophageal junction cancer","route":"/cancers/gastric/"},{"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/"}],"company":[{"id":"zymeworks","kind":"company","name":"Zymeworks","route":"/companies/zymeworks/"}]}}