Background: BPM 31510 targets the metabolic machinery of cancer cells to reverse the Warburg effect. The current study evaluates BPM 31510 as a 6-day continuous infusion as a single agent and in combination with 3 standard weekly chemotherapy regimens. The study was designed to determine the Phase II dose and infer multi-omic patient-centric signatures identifying molecular predictive markers of clinical benefit and patient stratification. Methods: Eligible patients (pts) (aged ≥ 18 y) were relapsed/refractory to standard therapy. The monotherapy arm received IV BPM 31510 for 6 d in continuous infusion in 28-d cycles, and combination arms (gemcitabine, 5-FU or docetaxel) were primed for 3 wks followed by weekly dosing in a 6 wk cycle. Doses were escalated in a 3+3 schema. Endpoints were safety, PK and multi-omics analysis. Tumor response is evaluated at wk 2 and then after every 2 cycles. Results: As of 10 Dec 2015, 85 pts have been enrolled. DLTs were reported at 171mg/kg in mono and at 137mg/kg in the gemcitabine arm (maximum administered dose) and were coagulopathy-related. Six of 66 pts (24%) maintained a minimum of Stable Disease for ≥ 4 cycles. Molecular signatures of response and safety were derived from the integrated omics and AI profiling of the Interrogative BiologyÒ platform. Biomarker candidates correlating with favorable clinical response and safety were identified. pK levels of BPM 31510 was a driver of favorable response. These molecular correlates were independent of tumor type and prior therapy indicating a broad anti-tumor effect of BPM 31510. Novel multi-omic panels could stratify response before and 24h post treatment with AUC > 0.85. Conclusions: BPM 31510 is well tolerated as a monotherapy and in combination with chemotherapeutic agents and associated with early anti-tumor activity. The MTD of 110mg/kg in the gemcitabine arm is being established and used in a planned Phase II pancreatic cancer trial. Dose-escalation in the other 3 arms is ongoing to determine phase II doses. Molecular signatures will be utilized in phase II trials to guide the patient stratification and selection for a variety of cancer types that will guide the development plan for BPM 31510 as anticancer agent. Clinical trial information: NCT01957735