Clinical Trials

Date: 2016-12-08

Type of information: Presentation of results at a congress

phase: preclinical

Announcement: presentation of results at the 17th International Association for the Study of Lung Cancer (IASLC) World Conference on Lung Cancer

Company: Spectrum Pharmaceuticals (USA - NV)

Product: poziotinib

Action mechanism: tyrosine kinase inhibitor. 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. Currently, poziotinib is being investigated by Hanmi in several mid-stage trials in different solid tumor indications including HER2-positive breast cancer.

Disease: lung cancer

Therapeutic area: Cancer - Oncology

Country:

Trial details:

Latest news:

• • On December 8, 2016, Spectrum Pharmaceuticals announced the oral presentation of data from a preclinical study evaluating poziotinib in lung cancer by scientists from MD Anderson Cancer Center at the 17th International Association for the Study of Lung Cancer (IASLC) World Conference on Lung Cancer which took place in Vienna, Austria, December 4-7, 2016.
• 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.

 

Is general: Yes