Discussion: Spectrum Pharmaceuticals (NASDAQ:SPPI) reported its plan to present updated data from a Phase 2 clinical trial of poziotinib in EGFR exon 20-mutant non-small cell lung cancer (NSCLC) at the World Conference on Lung Cancer in Toronto on September 24. Objective response rate (ORR) in the preliminary data of 40 patients is 58%. This is the first time trial data of Exon 20 insertion mutations are being released by the company. This particular subgroup is expected in about 3-5% of all NSCLC. The company claims that currently available treatments result in poor clinical result in these patients.

The present data set shows a marked decline of 6% from the April data in 11 patients. The disease control rate (DCR) and median progression-free survival rate stand at 90% and 5.6 months respectively. Among the HER-2 positive subgroup with exon 20-mutant NSCLC patients, the ORR and DCR data stood at 50% and 83% respectively. Even if 45% patients needed a dose reduction during the trial, there were no major adverse events. Almost 50% of those adverse events included skin rash, diarrhea and paronychia.

Poziotinib is a quinazoline-based tyrosine kinase inhibitor. As a tyrosine-kinase inhibitor (TKI), it irreversibly blocks signaling through the HER family of tyrosine-kinase receptors, including HER1, HER2, and HER4. The compound was described in its 1988 publication as the "tyrosine phosphorylation inhibitor". It also blocks epidermal growth factor receptor (EGFR) and HER2 mutations. In particular, tyrosine kinase enzymes activate many proteins through phosphorylation, in which a phosphate group is added to the protein. TKIs typically blocks this process of addition of phosphate and further signal transduction cascades. The company claims that the drug’s kinase-inhibiting capacities lead to blocking of downstream signaling and inhibition of the proliferation of tumor cells.