On October 4, 2019 Spectrum Pharmaceuticals, Inc. (NasdaqGS: SPPI), a biopharmaceutical company focused on novel and targeted oncology therapies, reported a publication from The University of Texas, MD Anderson Cancer Center entitled, "Pan-Cancer Landscape and Functional Analysis of ERBB2 Mutations Identifies Poziotinib as a Clinically Active Inhibitor and Enhancer of T-DM1 Activity (Press release, Spectrum Pharmaceuticals, OCT 4, 2019, View Source [SID1234540055])." The publication appears in the Oct 3, 2019 online issue at View Source(19)30384-8 and will be published in a future print issue of Cancer Cell.
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"Our analysis is the largest ever conducted to understand the diversity of HER2 mutations across 25 cancer types, including more than 200,000 patients from cBioPortal, MD Anderson, Foundation Medicine, and Guardant Health," said John Heymach, M.D., Ph.D., Chairman and Professor, Department of Thoracic/Head and Neck Medical Oncology at MD Anderson. "In our pre-clinical study of 11 EGFR/HER2 tyrosine kinase inhibitors, poziotinib was the most potent HER2 mutant-selective TKI tested, and in our initial clinical cohort we found that poziotinib was highly active in NSCLC patients with HER2 exon 20 mutations. Our findings indicate that poziotinib may be well-suited to target HER2 mutations with a constricted binding pocket. Furthermore, we have determined from pre-clinical data that poziotinib is synergistic with a HER2-targeting antibody-drug conjugate, providing a rationale for combinations to move forward into the clinic."
Spectrum is studying poziotinib in ZENITH20, a company-sponsored, open-label, single-arm, multi-center, global Phase 2 study of non-small cell lung cancer (NSCLC) patients.
"The publication of these latest research findings from MD Anderson on poziotinib in the journal Cancer Cell continues to strengthen the evidence of the potential benefit of poziotinib in the treatment of lung cancer," said Joe Turgeon, President and CEO, Spectrum Pharmaceuticals. "This quarter, we plan to disclose topline data from the first cohort of the company-sponsored ZENITH20 study, which is analyzing previously-treated NSCLC patients with exon 20 mutations in EGFR. By mid-2020 we also expect topline data from cohort 2, which is studying previously treated NSCLC patients with exon 20 mutations in HER2. We look forward to the top line data from the ZENITH20 study this quarter and continue to expand the poziotinib program, based on emerging science, to other areas of opportunity."
About Poziotinib
Poziotinib is a novel, oral epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) that inhibits the tyrosine kinase activity of EGFR (HER1) as well as HER2 and HER4. Importantly this 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.
Spectrum received exclusive license from Hanmi Pharmaceuticals to develop, manufacture, and commercialize poziotinib worldwide, excluding Korea and China. Poziotinib is currently being investigated by Spectrum and Hanmi in several trials in multiple solid tumors.
About ZENITH20
The ZENITH20 study consists of seven cohorts of NSCLC patients. Cohorts 1 (EGFR) and 2 (HER2) have completed enrollment of previously-treated NSCLC patients with exon 20 mutations. Cohort 3 (EGFR) and 4 (HER2) are currently enrolling first-line NSCLC patients with exon 20 mutations. Cohorts 1- 4 are each independently powered for a pre-specified statistical hypothesis and the primary endpoint is objective response rate (ORR). In July 2019, three new cohorts were added to the ZENITH20 study that are all currently enrolling patients. Cohort 5 includes previously treated or treatment-naïve NSCLC patients with EGFR or HER2 exon 20 insertion mutations. Cohort 6 includes NSCLC patients with classical EGFR mutations who progressed while on treatment with first-line osimertinib and developed an additional EGFR mutation. Cohort 7 includes NSCLC patients with a variety of less common mutations in EGFR or HER2 exons 18-21 or the extracellular or transmembrane domains.