Background: IM156 is a novel oral agent with a biguanide structure, which has anticancer activity through AMPK activation and reduction of oxidative phosphorylation. Inhibition of oxidative phosphorylation (OXPHOS) is detrimental to OXPHOS dependent drug resistant cancer cells which adapt metabolic shift upon cancer treatment or are intrinsically OXPHOS dependent cancer cells. OXPHOS dependent cancer cells are prone to energy stress such as OXPHOS inhibition that ultimately cause cancer cell death. Preclinical in vitro and in vivo experiments demonstrated that IM156 can be effective in glioblastoma, and other solid tumors. Therefore, a phase I dose-escalation study to determine safety and preliminary signals of activity of IM156 has been designed and activated (NCT03272256). Methods: This is an open label, single center, dose-escalation study using the 3+3 design to determine the maximum tolerated dose and/or recommended phase 2 dose, dose limiting toxicities (DLT), safety, pharmacokinetics, pharmacodynamics and preliminary signals of anticancer efficacy of IM156 in patients with advanced solid tumors refractory to standard therapies. Eligible patients are adults with advanced solid tumors refractory to standard therapies with adequate performance status (ECOG ≤2) and organ function with measurable disease per RECIST 1.1 (or RANO for gliomas). IM156 is administered orally every other day starting on day 1 of each 28 days cycle. The study has total of 6 dose levels ranging from 100 mg to 1,800 mg and the dose escalation continues per 3+3 design as long as the proportion of DLTs < 33% ( < 2/6). DLTs are evaluated during the first 28 days of therapy (cycle 1). Efficacy per RECIST 1.1 (RANO for gliomas) is evaluated every two cycles. Pharmacokinetics studies have been designed to determine Cmax, AUC, T1/2 and other parameters. Pharmacodynamics studies include PET scans with FDG and acetate probes, tissue and blood biomarkers including lactate levels. As of 2/8/18 the study enrolled 6 patients into two dose levels (100mg and 200mg respectively) and enrollment continues. Clinical trial information: NCT03272256