Background: ABTL0812 is a novel drug with reported preclinical activity in several tumor types. In vitro and in vivo assays have shown that ABTL0812 is an inhibitor of the Akt/mTOR pathway by a novel mechanism of action. Methods: A Phase I/Ib First in Human (FiH) clinical trial started on February 2014 (NCT02201823) in which patients with solid tumors and no standard treatment were enrolled. ABTL0812 was administered daily, by the oral route in 28-day cycles. The primary objective of the trial was to obtain a maximum tolerated dose and a recommended phase II dose (RP2D). The secondary objectives of the trial were assessment of dose-limiting toxicity (DLT), response rate, progression-free survival and overall survival. Pharmacokinetic (days 1 and 29) and pharmacodynamic (inhibition of the phosphorylation of Akt in platelets at day 29 vs. predose, as biomarker) end-points were also introduced. The study design consisted in a 3+3 dose escalation with up to five cohorts. An expansion phase with 12 patients is planned. Results: The dose-escalation, in which 15 patients were recruited, started at 500 mg/day and was completed in December 2014 at 4,000 mg/day. ABTL0812 showed overall a good safety profile. Grade 1-2 adverse events included swallowing disturbance, asthenia, increase of hepatic enzymes, hyperglycemia and nausea; grade > 2 adverse events were rare and included anemia and asthenia. No DLTs were observed and therefore, RP2D has been determined as 1,300 mg tid by pharmacokinetic-pharmacodynamic modeling of drug plasma concentrations at steady state vs. platelet pAkt inhibition. One patient with endometrial cancer and one patient with sigmoid colon cancer currently show stable disease (SD) after 10 and 5 months of treatment, respectively. Conclusions: RP2D of ABTL0812 has been determined. ABTL0812 has demonstrated a good safety profile, with only mild adverse events. Additionally, ABTL0812 has shown activity on biomarkers, and hints of activity in two patients presenting prolonged SD. Clinical trial information: NCT02201823