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. Potent inhibition was observed in cell lines resistant to rapamycin and pan-PI3K inhibitors.
Unlike other drugs targeting this pathway, INK128 inhibits the kinase activity associated with both the TORC1 and TORC2 complexes of the mTOR kinase. This dual TORC1 and TORC2 activity differentiates INK128 from rapamycin and various related analogs, or rapalogs, which only interfere with TORC1 activity, allowing for feedback loops that may actually augment tumor growth. In contrast, inhibition of both TORC1 and TORC2 may allow for improved efficacy and ultimately greater therapeutic potential for patient benefit.
The Phase I program includes several clinical trials:
Advanced Solid Malignancies: A Phase I dose escalation study is currently underway 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.
Multiple Myeloma and Waldenstrom’s Macroglobulinemia: A Phase I dose escalation study is currently underway to evaluate the safety, tolerability and pharmacokinetics of single-agent INK128 in patients with Multiple Myeloma and Waldenstrom’s Macroglobulinemia. This trial is being conducted with the support of the Multiple Myeloma Research Foundation as part of its Biotech Investment Award research award program.
Combination Study with Paclitaxel: A phase Ib combination safety study is currently underway to evaluate the safety, tolerability and pharmacokinetics of INK128 combined with paclitaxel and with and without Trastuzumab in patients with advanced solid tumors.