First-In-Man Clinical Trial of the Oral Pan-AKT Inhibitor MK-2206 in Patients With Advanced Solid Tumors

    December 2011 in “ Journal of clinical oncology ”
    Timothy A. Yap, Yan Li, Amita Patnaik, Ivy Fearen, David Olmos, Kyriakos P. Papadopoulos, Richard D. Baird, Liliana Delgado, Akosha Taylor, Lisa C. Lupinacci, Ruth Riisnaes, Lorna Pope, Simon P. Heaton, George V. Thomas, Michelle D. Garrett, Daniel M. Sullivan, Johann S. de Bono, Anthony W. Tolcher
    TLDR MK-2206 was safe and effectively blocked AKT signaling in cancer patients, warranting more trials.
    The first-in-man clinical trial of the oral pan-AKT inhibitor MK-2206 in 33 patients with advanced solid tumors established the maximum-tolerated dose at 60 mg due to dose-limiting toxicities like skin rash and stomatitis. MK-2206 was generally well-tolerated and showed evidence of AKT signaling blockade, with significant declines in phosphorylated AKT in tumor biopsies and suppression in hair follicles. Preliminary antitumor efficacy was observed, including a notable case of a patient with pancreatic adenocarcinoma showing a 60% decrease in cancer antigen 19-9 levels and 23% tumor shrinkage. The results supported further rational combination trials to enhance clinical benefits.
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