Poziotinib (HM781-36B): Pharmacokinetics, Applications in the Treatment of Non-Small-Cell Lung Cancer and Dosage

Poziotinib is a pan-human epidermal growth factor receptor (HER) inhibitor that irreversibly blocks the signaling pathways of EGFR, HER2, and HER4, exerting an anti-tumor effect. In vitro studies have demonstrated that poziotinib exhibits remarkable selectivity and efficacy against EGFR ex20ins mutations compared to traditional EGFR TKIs.

Pharmacokinetics of Poziotinib

Poziotinib is a novel, oral, irreversible TKI with a unique structure that allows for binding of HER2 receptors that have exon 20 insertion mutations. Insertion mutations in exon 20 of HER2 cause steric hindrance in the kinase domain, which renders available TKIs significantly less effective.

Applications in the treatment of Non-Small-Cell Lung Cancer

Poziotinib is an orally available quinazoline-based EGFR inhibitor. In vitro, poziotinib had an average IC50 value of 1.0 nM in Ba/F3 cell lines with an EGFR ex20ins mutation, making poziotinib approximately 100 times more potent than osimertinib and 40 times more potent than afatinib.In a phase I trial, poziotinib reported encouraging efficacy in EGFR-mutant NSCLC and HER2-amplified breast or stomach cancers. The most common AEs were diarrhea, skin rash, stomatitis and pruritus.¹

Dosage of Poziotinib

The recommended dosage for poziotinib is 16 mg orally QD. Reductions in dose are recommended to manage adverse reactions.

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