Poziotinib
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.
Overview
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.
- ATP pocket
- Inhibitor blocks phosphotransfer
- Kinase domain
1.Poziotinib slips into a pocket on HER2.
- AmivantamabApproved
- CamizestrantApproved
- Comprehensive genomic profilingStandard of care
- Liquid biopsy (ctDNA)Standard of care
- LorlatinibApproved
- MRD / molecular residual disease testingEstablished
- ADC payload neutralisersPhase 1
- BGB-16673Phase 3
- Bispecific ADCPhase 3
- BRUIN CLL-321Positive
- CaDAnCe-304Recruiting
- CIRCULATE-Japan (GALAXY / VEGA / ALTAIR)Active
- A clone report from blood at every treatment cycle
- A fast route to the matched drug when it is licensed for another cancer
- A multi-cancer platform trial of adaptive (dose-holiday) therapy
- A national rapid research autopsy network for end-stage cancer
- A standard evolvability score for every tumour
- A standing platform trial that assigns treatment by how the tumour escaped
Background: ADC sequencing, Antigen escape (antigen loss, lineage switch), BCG-unresponsive, Castration-resistant prostate cancer (CRPC), Circulating tumour DNA (ctDNA). Also on OnCo: Resistance atlas · Lines of therapy.
Trials
topTrials recruiting now
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Latest papers
topQuery 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.
Similar pages
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- PersonFei Ma