Phase I pharmacokinetic and pharmacodynamic study of the inhibitor of activation of AKT (p-Akt), triciribine phosphate monohydrate (TCN-PM), in solid malignancies

B71 Background: AKT is an important signal transduction kinase that is frequently dysregulated, and occasionally mutated, in cancer cells. Triciribine phosphase monohydrate (TCN-PM) is a tricyclic nucleoside that inhibits the levels of phosphorylated AKT (p-Akt) and suppresses selectively the growth of tumors with hyperactivated pAkt. Methods: We conducted a phase I dose escalation study of TCN-PM administered intravenously weekly over one hour days 1, 8 and 15, with treatment cycles every 28 days, in adult subjects with advanced solid tumors refractory to standard therapy, whose tumors had been demonstrated to have high levels of p-Akt by immunohistochemistry (IHC). Tumor biopsies were obtained prior to initiation of therapy and on day +16, and assessed for the presence of p-Akt by IHC and Western blot analysis. Results: Thirteen subjects have enrolled to date (M:F 5:8, mean age 60 years, range 46-81): eight subjects are evaluable for radiopgraphic response (see table below). Conclusions: Toxicity has been modest at the doses evaluated to date: accrual is ongoing. Updated pharmacokinetic and pharmacodynamic data will be presented at the meeting.