ArQule, Inc. announced new clinical and preclinical data demonstrating the potential of the company’s AKT inhibitor ARQ 751 in treating solid tumors characterized by mutations in the PI3K/AKT/mTOR pathway. The findings were detailed in two poster presentations at the 2019 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics. A poster entitled “The use of biomarkers and ctDNA in a phase 1 trial of ARQ 751” detailed the molecular profiling of a subgroup of patients in the phase 1 clinical trial of ARQ 751 in solid tumor indications characterized by AKT, PIK3CA or PTEN mutations. Key findings suggest that ctDNA could be a valuable measure of patient response to ARQ 751. Specific highlights include: There is a high concordance (76%) between the pre-study mutation and the mutation as measured using ctDNA profiling; Though patient data are limited, analysis of the correlation between ctDNA mutational status and patient response suggest that PIK3CA H1047R has prognostic value; ARQ 751 exposure correlates with glucose and insulin levels and indicates on-target engagement. A poster entitled “In vitro and in vivo combination of ARQ 751 with PARP inhibitors, CDK4/6 inhibitors, Fulvestrant and Paclitaxel” details preclinical findings from studies of ARQ 751 treatment in combination with a variety of therapeutic agents, in experimental breast cancer models. Overall, data show that the addition of any of the evaluated agents enhances the activity of ARQ 751 in vivo and in vitro and support the therapeutic potential of ARQ 751. Specific highlights include: The combination of ARQ 751 with an ER antagonist (fulvestrant) or a CDK4/6 inhibitor (palbociclib) or with both agents showed enhanced anti-tumor activity in comparison to the single agents and enhanced pathway inhibition in vivo. A combination of ARQ 751 with both agents showed tumor regression in vivo. The combination of ARQ 751 with chemotherapy (paclitaxel) showed enhanced anti-tumor activity in comparison to single agents in vivo. The combination of ARQ 751 with PARP inhibitors (olaparib, talazoparib, rucaparib) showed enhanced anti-proliferative activity in vitro. A phase 1b clinical study of ARQ 751 in a molecularly defined patient population as single agent or in combination with fulvestrant or paclitaxel is ongoing (NCT02761694).