Bayesian Ai To Delineate Molecular Signatures Of Patient Susceptibility To Potential Hematologic Events In A Phase I Study Of Bpm31510 (Ubidecarenone) In Solid Tumors.

e14042 Background: BPM 31510 is a ubidecarenone containing nanodispersion elicits anticancer effect by switching cancer cells energy generation from glycolysis to mitochondrial OXPHOS; i.e. reverses Warburg effect. This Phase 1 study is evaluating safety of 144-hour infusion of BPM 31510 as a single agent and in combination with 3 standard chemotherapy regimens. The molecular adaptive study design enabled longitudinal multi-omic molecular profiling to delineate personalized cause-and-effect networks relating patient biology to clinical outcomes using unbiased Bayesian statistics based bAIcis Artificial Intelligence (AI) technology Methods: Eligible pts (aged ≥ 18 y) were relapsed/refractory to standard therapy. The monotherapy arm received IV BPM31510 for 144-hour infusion in 28d cycles, and combination arms (gemcitabine, 5-FU or docetaxel) were primed with BPM 31510 for 3 wks followed by weekly dosing in a 6wk cycle. Doses were escalated in a 3+3 schema. Endpoints were safety, PK and multi-omics analysis. Clinical information was processed and integrated with multi-omic molecular data (metabolomics, lipidomics and proteomics), utilized bAIcis to learn relationships and extract actionable information from pt records, molecular features and corresponding clinical response. Results: As of 10 Dec 2016, 97 pts have been enrolled. Hematologically-related DLTs were reported at 171mg/kg in monotherapy and 137mg/kg in the BPM31510+gemcitabine arm (maximum administered dose). The bAIcis-generated set of predictors defining coagulation-related events in the clinical trial population include proteins, lipids, and metabolites, the levels of which can potentially predict undesirable events prior to and 24h after the 1 st treatment with BPM 31510. Conclusions: BPM31510 is well tolerated as a monotherapy and in combination with chemotherapeutic agents. Molecular signatures of susceptibility have been identified through use of multi-omic based AI analysis. Molecular signatures predictive of coagulation-related events will be assessed in Phase 2 and 3 trials to guide the development plan for BPM 31510 as anticancer agent. Clinical trial information: NCT01957735.