Spectrum Pharmaceuticals Highlights Promising Preclinical Data Evaluating Poziotinib in Lung Cancer at the 17th IASLC World Conference on Lung Cancer
- Pre-clinical results show poziotinib could potentially be effective in patients with non-small cell lung cancer with EGFR exon 20 mutations.
- Computational modeling suggests that due to its small size, poziotinib may overcome the steric hindrance of the drug binding pocket.
- An investigator sponsored clinical trial testing poziotinib in EGFR exon 20 mutant non-small cell lung cancer patients is expected to begin enrollment soon to investigate this hypothesis.
"We are honored to have an oral presentation on poziotinib presented at
Abstract/Oral Presentation #6203: Drug Repurposing to Overcome De Novo Resistance of Non-Traditional EGFR Mutations: Poziotinib inhibits EGFR exon 20 insertion mutations in NSCLC
EGFR exon 20 insertions induce a shift in the structure of cancer cells that prevents binding of many EGFR inhibitors. In vitro, Ba/F3 cells with EGFR exon 20 insertions were screened against several EGFR inhibitors including erlotinib, gefitinib, afatinib, dacomitinib, neratinib, poziotinib, ibrutinib rocilentinib, EGF816, and osimertinib. In Ba/F3 cells with EGFR exon 20 insertions, most of the TKIs failed to inhibit growth of EGFR exon 20 insertions with IC50 values above 100nM. However, poziotinib significantly inhibited cell growth of all EGFR exon 20 insertions tested with an average IC50 value of 2.9nM, as compared to osimertinib and rocilentinib (IC50 values =103nM and 850nM, respectively). In vivo, poziotinib reduced ≥80% of tumor burden in multiple mouse models. Computational modeling suggests that its smaller structure gives poziotinib the potential to overcome the steric hindrance of the drug binding pocket. An investigator sponsored clinical trial testing poziotinib in EGFR exon 20 mutant NSCLC patients is expected to begin enrollment soon.
Poziotinib is a novel, oral pan-HER inhibitor that irreversibly blocks
signaling through the Epidermal Growth Factor Receptor (EGFR, HER)
Family of tyrosine-kinase receptors, including HER1 (erbB1; EGFR), HER2
(erbB2), and HER4 (erbB4), and importantly, also HER receptor mutations;
this, in turn, leads to the inhibition of the proliferation of tumor
cells that overexpress these receptors. Mutations or
overexpression/amplification of EGFR family receptors have been
associated with a number of different cancers, including non-small cell
lung cancer (NSCLC), breast cancer, and gastric cancer. Currently,
Poziotinib is being investigated by Hanmi in several mid-stage trials in
different solid tumor indications including HER2-positive breast cancer.
(Phase 2 sponsored by National OncoVenture, a funding initiative by the
Spectrum Pharmaceuticals is a leading biotechnology company focused on acquiring, developing, and commercializing drug products, with a primary focus in Hematology and Oncology. Spectrum currently markets six hematology/oncology drugs, and has an advanced stage pipeline that has the potential to transform the Company. Spectrum's strong track record for in-licensing and acquiring differentiated drugs, and expertise in clinical development have generated a robust, diversified, and growing pipeline of product candidates in advanced-stage Phase 2 and Phase 3 studies. More information on Spectrum is available at www.sppirx.com.
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