Abexinostat (Abx) As A Means To Reverse Pazopanib (Paz) Resistance: A Phase 1 Study In Advanced Solid Tumor Malignancies.

2519Background: PAZ is a tyrosine kinase inhibitor of VEGFR approved for use in renal cell carcinoma (RCC). ABX is a potent pan-HDAC inhibitor (HDACi). Pre-clinical models suggest that HDACi-mediated epigenetic modulation of VEGF expression prevents PAZ resistance and potentiates efficacy. We therefore designed a Phase I clinical trial combining ABX with PAZ in pts with advanced solid tumors with an expansion cohort in RCC. Methods: The primary endpoint was the maximal tolerated dose (MTD) of PAZ plus ABX. Secondary endpoints included pharmacokinetics (PK) and efficacy. PAZ was dosed days 1-28 and ABX days 1-5, 8-12, and 15-19 of 28-day cycle (schedule A) with at a starting dose of 400 mg/day and 45 mg/m2orally twice daily respectively. An alternate ABX dosing schedule days 1-4, 8-11, and 15-18 was investigated (schedule B) due to toxicity of Schedule A. Results: 52 patients (pts) (RCC; N = 23) with advanced solid tumors were enrolled (N = 22 schedule A; N = 30 schedule B). There were six dose-limiting to...