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Poziotinib Shows Promise in Hard-to-Treat NSCLC Exon 20 Mutations

Rachel Narozniak
Published: Tuesday, Sep 03, 2019

Nishan Tchekmedyian, MD, principal investigator on the ZENITH20 trial

Nishan Tchekmedyian, MD

Poziotinib, a novel drug that targets relatively uncommon EGFR and HER2 exon 20 insertion mutations, is being tested in a biomarker-driven trial of patients with non–small cell lung cancer (NSCLC) in both second-line and treatment-naïve settings.

“Poziotinib is one of the first molecules that we’ve realized as capable of overcoming steric hindrance, which essentially blocks all other TKIs’ ability to bind effectively,” Tchekmedyian said. “By virtue of the fact that it’s microscopically smaller and less rigid than other TKIs, poziotinib can fit into the drug-binding pocket that usually shuts out all of the other TKIs that we have available. We need an agent that gets into the drug binding pocket and binds consistently to provide the inhibition that will then cause tumors to shrink.”

Figure. Poziotinib in NSCLC With EGFR or HER2 Exon 20 Insertion Mutation

Figure. Poziotinib in NSCLC With EGFR or HER2 Exon 20 Insertion Mutation
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