Background: BPM31510-IV is an Ubidecarenone (CoQ10) containing IV nanodispersion targeting metabolic machinery in cancer, shifting bioenergetics from lactate dependency towards mitochondrial OxPhos and reversing the Warburg effect. This study evaluated the safety & tolerability of BPM 31510-IV alone or in combination with chemotherapy. The study design included PD sampling for multi-omic analysis to identify predictive markers of clinical benefit and patient stratification. Methods: Eligible patients 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 with BPM31510 prior to chemotherapy regimen followed by weekly dosing in a 6 wk cycle. Endpoints were safety, pharmacokinetics (PK) and pharmacodynamics (PD). Tumor response was evaluated at cycle 1 and then after every 2 cycles. Results: A total of 98 pts were enrolled. Thirty of 66 evaluable pts (45%) achieved stable Disease, for ≥ 2 cycles and 16/66 (24%) maintained a minimum of SD for ≥ 4 cycles. 99% patients receiving ≥ 1 treatments with BPM31510 experienced a TEAE. The most frequently experienced TEAEs were asymptomatic elevated APTT in 80% of pts, INR increased in 74%, PTT prolonged 64%, Anemia in 41%, fatigue in 24% and both AST increase & platelet decrease in 16% of pts. Molecular predictors of coagulation-related events prior to and 24h after 1^st treatment with IP were identified. Biomarker candidates correlating with favorable clinical response & safety identified were independent of tumor type and prior therapy, suggesting a broad anti-tumor effect. Novel multi-omic panels with potential to stratify response before and 24h post treatment with AUC > 0.85 were identified. Conclusions: BPM31510-IV is well tolerated as monotherapy and in combination with several standard chemotherapeutic agents. Molecular signatures with predictive potential of the safety and clinical response have been identified that will guide Phase 2/3 clinical development. Clinical trial information: NCT01957735