Under Clinical Evaluation
The PI3K/Akt/mTOR pathway is frequently dysregulated in human cancer, providing a rationale for why mTOR kinase has become one of the most important molecular targets for oncology drug development.
INK128 is an orally-available, potent and selective TORC1/2 inhibitor with outstanding drug-like properties. INK128 has demonstrated broad preclinical anti-tumor activity against a range of solid tumor types. Oral administration of INK128 inhibited angiogenesis and tumor growth in multiple preclinical models with predicted dose-exposure relationship. Potent inhibition was also observed in cell lines resistant to rapamycin and pan-PI3K inhibitors.
Unlike other drugs targeting the pathway, INK128 directly inhibits the activity associated with both the TORC1 and TORC2 complexes of the mTOR kinase. This direct inhibition and dual activity differentiates INK128 from rapamycin and related analogs, or rapalogs, which predominately modulate TORC1 activity. In contrast, by inhibiting both TORC1 and TORC2, INK128 more potently inhibits mTOR kinase and may provide for greater efficacy.
The Phase I trial is a dose escalation study to evaluate the safety, tolerability and pharmacokinetics of single-agent INK128 in patients with advanced solid tumors. The study will also evaluate pharmacodynamic correlation between INK128 exposure and upstream or downstream markers of the mTOR pathway as well as candidate predictive markers.