Phase I Study Of Opb51602, A Small Molecule Inhibitor Of Stat3 Phosphorylation, In Patients With Refractory Solid Malignancies

3002 Background: STAT3 is constitutively activated by growth signaling pathways in many malignancies; in many cell lines inhibition of STAT3 leads to cell death. OPB51602 is a small molecule inhibitor of STAT3 phosphorylation (Tyr705) and activation. Methods: A phase I study of OPB51602 administered for 2 weeks every 3 weeks was initiated to determine the maximum tolerable dose (MTD), evaluate pharmacokinetics (PK), and assess pharmacodynamics effects on STAT3 in peripheral blood mononuclear cells (PBMCs). The starting dose was 2mg/day, and dose escalations to 5mg/d, 10mg/d, 20mg/d, were planned. Single dose PK was done on the first day of administration for 4 days. Dose escalation was based on the “3+3” design, MTD was defined as the dose with at least 2/6 dose limiting toxicities (DLTs) in the first cycle and toxicities were graded by NCICTCv4.0. Results: 32 patients (pt) were treated at doses of 2mg/d (n=7), 4mg/d (n=18), 5mg/d (n=7). The main toxicities observed included nausea/vomiting, diarrhea, per...