{"entity":{"id":"poziotinib","kind":"drug","name":"Poziotinib","aka":["HM781-36B","NOV120101"],"tldr":"Poziotinib was a tablet designed to fit the awkward shape of HER2 and EGFR exon 20 mutations in lung cancer. It shrank tumours in some patients but caused severe rash and diarrhoea, and the FDA declined to approve it in 2022.","summary":"Poziotinib was discovered by Hanmi Pharmaceutical and developed in the West by Spectrum Pharmaceuticals. Its selling point was activity against exon 20 insertion mutations, which resist earlier EGFR and HER2 kinase inhibitors. In the ZENITH20 trials in HER2 exon 20-mutant non-small-cell lung cancer, response rates were around 28 to 35 percent, but grade 3 rash, diarrhoea and stomatitis were common and most patients needed dose reductions.\n\nAn FDA advisory committee voted against approval in September 2022, citing modest benefit, toxicity and the availability of trastuzumab deruxtecan, and the agency issued a complete response letter in November 2022; Spectrum then stopped development. The HER2-mutant lung cancer page lists it with pyrotinib among the HER2 kinase inhibitors limited by EGFR-driven side effects.","status":"negative","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Poziotinib","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Poziotinib"}],"tags":["subtype-drugs-wave"],"related":["pyrotinib","trastuzumab-deruxtecan"],"cancers":["her2-mutant-nsclc"],"sections":[],"technologies":["her2-tyrosine-kinase-inhibitors"],"targets":["her2","egfr"],"drugs":[],"companies":["spectrum-pharmaceuticals"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"code":"HM781-36B","modality":"Oral irreversible pan-HER tyrosine kinase inhibitor","mechanism":"An irreversible inhibitor of EGFR, HER2 and HER4 whose small, flexible structure was designed to fit the narrowed drug-binding pocket created by exon 20 insertion mutations in HER2 and EGFR.","approvals":[],"mechanismSteps":[],"toxicity":[],"access":[],"regulatoryEvents":[]},"route":"/drugs/poziotinib/","neighbours":{"drug":[{"id":"pyrotinib","kind":"drug","name":"Pyrotinib","route":"/drugs/pyrotinib/"},{"id":"trastuzumab-deruxtecan","kind":"drug","name":"Trastuzumab deruxtecan","route":"/drugs/trastuzumab-deruxtecan/"}],"cancer":[{"id":"her2-mutant-nsclc","kind":"cancer","name":"HER2-mutant non-small-cell lung cancer","route":"/cancers/her2-mutant-nsclc/"}],"technology":[{"id":"her2-tyrosine-kinase-inhibitors","kind":"technology","name":"HER2 tyrosine kinase inhibitors","route":"/technologies/her2-tyrosine-kinase-inhibitors/"}],"target":[{"id":"egfr","kind":"target","name":"EGFR","route":"/targets/egfr/"},{"id":"her2","kind":"target","name":"HER2","route":"/targets/her2/"}],"company":[{"id":"spectrum-pharmaceuticals","kind":"company","name":"Spectrum Pharmaceuticals","route":"/companies/spectrum-pharmaceuticals/"}]}}