Background: BPM 31510 is a small molecule that targets the metabolic machinery of the cancer microenvironment to create a hallmark shift from lactate dependency towards mitochondrial oxidative phosphorylation, reversing the Warburg effect. Preclinical data indicate BPM 31510 causes this shift resulting in tumor regression and enhances the antitumor activity in combination with chemotherapy agents in a priming schedule. This is the first clinical study to evaluate BPM 31510 at a 4-days (d) continuous infusion in four arms; as a single agent, and in combination with Gemcitabine, 5-FU or Docetaxel. Methods: Eligible patients (pts) (aged ≥ 18 y) had previously treated relapsed/refractory ST. Pts in the monotherapy arm received IV BPM 31510 for 4 d in continuous infusion in 28-d cycles. Pts in the combination arms were primed for 3 wks and then started in a weekly dosing (either gemcitabine, 5-FU or docetaxel) after the BPM 31510 infusion in a 6-wk cycle. Doses were escalated in a 3+3 schema. Phase I endpoints were safety, PK and Multi-Omics based pharmacodynamics. Tumor response is evaluated at wk 2 and every 4 -6 wks. Results: As of 01 Dec 2014, 56 pts have been enrolled. Pts have been treated at 3 dose levels up to 137 mg/kg. No DLTs or treatment‐related SAEs have been reported. MTD has not yet been established. Most frequently reported related AEs in all 4 arms were grade 1-2 INR prolongation that resolved after Vitamin K administration. No bleeding reported. Grade 1-2 thrombocytopenia has been seen in the Gemcitabine arm requiring dose modification. PK data indicated linear distribution. 12/25 pts (48%) that are evaluable for efficacy after cycle 2 showed various responses including: tumor reductions, decrease FDG, arrested tumor progression, stable disease, decrease in tumor markers, QOL improvements. Integrated multi-omics technology showed reversal of the Warburg effect in selected pts. Conclusions: Emerging data from this study suggest that BPM 31510 is well tolerated in monotherapy or in combination with chemotherapy agents. Early anti-tumor activity is seen. Dose-escalation on a 6-day infusion schedule is ongoing to determine the recommended phase II dose Clinical trial information: NCT01957735