The drug, known as MK-2206, can shut down cancer cell growth, survival, and metabolism, and reverse resistance to currently used anti-cancer drugs, by stopping the function of an important signalling molecule called AKT. This research builds on previous work carried out at The Institute of Cancer Research, London, and The Royal Marsden NHS Foundation Trust, which tested MK-2206 as a single agent.
Study leader Dr Rhoda Molife, Senior Investigator at the Institute of Cancer Research (ICR) and Medical Oncologist at The Royal Marsden, said: “This is the first published study combining an AKT inhibitor with other anti-cancer drugs. It allowed us to determine the safety of these drug combinations and to define and recommend doses for phase II studies.”
The multicentre, phase I study investigated the safety and tolerability of MK-2206 when used in combination with other chemotherapy agents – carboplatin and paclitaxel, docetaxel, or erlotinib.
The researchers found that MK-2206 could be combined safely with the different drugs, using intermittent schedules. There was also tantalising evidence of anti-tumour activity, most notably in combination with carboplatin and paclitaxel, even when patients had previously received and failed to adequately respond to these same chemotherapies.
The safety data allowed the researchers to recommend doses of MK-2206 for use in phase II studies, which will determine the effectiveness of the new combinations.
Dr Molife said: “The doses and schedules defined in our study formed the basis of dosing in the current phase II studies. Some of these studies are combining MK-2206 with different drugs; however, the premise remains the same – testing MK-2206 in combination with other drugs is clinically relevant and should these phase II studies be successful, another treatment option for cancer patients may become available in the future.”
- Molife, LR., Yan, L., Vitfell-Rasmussen, J., Zernhelt, AM., Sullivan, DM., Cassier, PA., Chen, E., Biondo, A., Tetteh, E., Siu, LL., et al. (2014) Phase 1 trial of the oral AKT inhibitor MK-2206 plus carboplatin/paclitaxel, docetaxel, or erlotinib in patients with advanced solid tumors. Journal of Hematology & Oncology, 7:1 doi:10.1186/1756-8722-7-1