ARIAD Pharmaceuticals recently revealed results of its investigational tyrosine kinase inhibitor (TKI), AP32788, that is designed to target specific mutations in patients with non-small cell lung cancer (NSCLC) but without available therapies.
The data, included in an oral presentation titled, “AP32788, a potent, selective inhibitor of EGFR and HER2 oncogenic mutants, including exon 20 insertions, in preclinical models,” were presented in April at the American Association for Cancer Research (AACR) Annual Meeting 2016, in New Orleans, La.
According to the American Cancer Society, NSCLC is the most common type of lung cancer and accounts for about 85% of lung cancer cases in the U.S. In 2015, an estimated 221,200 patients were diagnosed with the disease.
NSCLC is caused primarily by mutations in the EGFR gene found in cell surface protein that binds to epidermal growth and promotes cell proliferation. Therapeutically, the most common EGFR mutations are treated by approved TKI target therapies, but about 4 to 9% of EGFR-mutated lung cancers with exon 20 insertion mutations have no available therapies.
AP32788 is an investigational oral TKI drug designed to target particular mutations in genes EGFR or HER2 induced by exon 20 insertion mutations that affect NSCLC patients who currently have no treatment options.
The results from the preclinical studies revealed that the drug AP32788 inhibited all EGFR and HER2 mutations tested in engineered cell lines, including exon 20 insertion mutants. Inhibition of wild-type (WT) EGFR in non-tumor cells was linked to dose-limiting toxicities of EGFR inhibitors. AP32788 is found to induce irreversible inactivation of EGFR exon 20 with 20-fold selectivity over WT EGFR, when compared to other tested EGFR TKIs. Additionally, tolerated doses of AP32788 led to regression of tumors in the mouse model of EGFR exon 20.
“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 press 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.”
The Phase 1/2 clinical trial of AP32788 will start enrolling patients during the second quarter of 2016.
ARIAD Pharmaceuticals is an orphan oncology company focusing on novel treatments for different forms of chronic and acute leukemia, lung cancer and other difficult-to-treat orphan cancers.