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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.
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.
An 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.
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. Connects to HER2 and EGFR.
1.Poziotinib slips into a pocket on HER2.
Background: ADC sequencing, Antigen escape (antigen loss, lineage switch), BCG-unresponsive, Castration-resistant prostate cancer (CRPC), Circulating tumour DNA (ctDNA). Also on OnCo: Resistance: how tumours escape each drug class · Lines of therapy.
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Query for this drug: (TITLE:"Poziotinib" OR ABSTRACT:"Poziotinib" OR TITLE:"HM781-36B" OR ABSTRACT:"HM781-36B" OR TITLE:"NOV120101" OR ABSTRACT:"NOV120101") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about Poziotinib, not a curated reading list.
Shares Trastuzumab deruxtecan, HER2 and the tag subtype-drugs-wave.
Shares EGFR and the tag subtype-drugs-wave.
Shares HER2 tyrosine kinase inhibitors, HER2-mutant non-small-cell lung cancer, Trastuzumab deruxtecan, HER2.
Shares HER2-mutant non-small-cell lung cancer, EGFR, HER2.
Shares HER2-mutant non-small-cell lung cancer, EGFR, HER2.
Shares HER2-mutant non-small-cell lung cancer, Trastuzumab deruxtecan, HER2.