ARIAD Pharmaceuticals, a pharmaceutical company dedicated to discovering innovative medicines for the improvement of cancer patients, recently presented preclinical study results of its investigational drug AP32788, a tyrosine kinase inhibitor (TKI) targeting specific gene mutations in certain patients suffering from non-small cell lung cancer (NSCLC). The results showed the drug’s potential as a therapeutic agent for a currently unmet medical need.
The data was presented at the American Association for Cancer Research (AACR) Annual Meeting 2016, under the title “AP32788, a potent, selective inhibitor of EGFR and HER2 oncogenic mutants, including exon 20 insertions, in preclinical models.”
According to the American Cancer Society, NSCLC accounts for 85 to 90 percent of all cases of diagnosed lung cancer. Mutations in the epidermal growth factor receptor (EGFR) gene are the largest known targetable subset of NSCLC tumors. The most common types of EGFR mutations have been addressed by other TKI therapies, but about 4 to 9 percent of EGFR-mutated lung tumors with exon 20 insertion mutations remain without targeted therapy options. Moreover, patients with mutations in the human epidermal growth factor receptor 2 (HER2) gene, which comprise approximately 2 percent of NSCLC patients, also have no treatment options available.
The data recently presented showed that AP32788 was able to inhibit all tested EGFR and HER2 mutants, including exon 20 insertion mutants, with selectivity over wild-type (WT) EGFR, in a set of engineered cell lines. AP32788 irreversibly inactivated EGFR exon 20 with 20-fold selectivity over WT EGFR, compared to other tested EGFR TKIs. The selective inhibition of WT EGFR has been associated with dose-limiting toxicities of EGFR inhibitors in patients. Importantly, the drug also induced tumor regression in a mouse model of the condition, with good tolerability results.
“These preclinical data on AP32788 demonstrate its potential to potently inhibit exon 20 mutant forms of EGFR and HER2, that are not addressed by currently available TKI treatments,” said Timothy P. Clackson, president of research and development and chief scientific officer at ARIAD, in a news release. “The selectivity data suggest that efficacious levels of exposure to AP32788 may be achievable in patients with these challenging mutations — a hypothesis we will be testing in the Phase 1/2 trial. We believe AP32788 is the first TKI that has been designed and optimized to inhibit the underlying mutation present in these orphan oncology disease subsets.”