INK1117 is an orally-available, small molecule inhibitor of the PI3Kα-isoform for the treatment of solid tumor malignancies.
The PI3K/Akt/mTOR pathway is frequently upregulated and/or dysregulated in human tumors and PI3Ks are important regulators of cancer-related pathways involved in cell proliferation, adhesion, survival and motility. The PIK3CA gene encoding the p110α catalytic subunit, represents one of the most highly mutated oncogenes identified in human cancers and is frequently mutated in a broad spectrum of tumors including breast, colon, brain and lung. While pan-PI3K inhibitors are currently being tested in the clinic, more PI3Kα isoform-specific inhibition holds promise as a next generation rationalized molecular targeted therapeutic strategy offering personalized cancer medicine.
INK1117 has demonstrated significant efficacy in several PI3Kα mutant-specific preclinical mouse xenograft tumor models. Moreover, daily oral administration of INK1117 inhibited tumor growth in a dose-dependent manner with a predicted PK/PD relationship, was well tolerated at a range of efficacious doses, and exhibited several differentiating features from less selective inhibitors that target the PI3K/Akt/mTOR pathway.
A Phase I dose escalation study is underway to evaluate the safety, tolerability and pharmacokinetics of single-agent INK1117 in patients with advanced solid malignancies who have tumors characterized by the presence of a PIK3CA mutation.