Results of a study of the oral inhibitor PTC299 on tumor VEGF synthesis.

3069 Background: Antiangiogenic drugs interfere with the VEGF signaling pathway. PTC299, an oral investigational drug, is designed to inhibit the synthesis of VEGF and other angiogenic cytokines in tumors. In models of human cancer xenografts in mice, single‐agent PTC299 decreases intratumoral and circulating VEGF levels and results in regression, eradication, or delay of tumor growth. This report analyzes the effect of single-agent PTC299 on human serum VEGF (sVEGF) in patients (pts) with advanced solid tumors. Methods: In stage 1 of this phase Ib study, monotherapy was given 4 weeks on and 2 weeks off at escalating weight-based doses 0.3, 0.6, and 1.2 mg/kg BID. In stage 2, monotherapy was given continuously with escalating unit dosing of 100 mg BID followed by cohorts at 100, 120, 160, and 200 mg TID. Treatment continued to disease progression. Safety, PK, and clinical activity were assessed; sVEGF levels were obtained Day 1 (D1) and Day 42 (D42). Results: Stages 1 and 2 enrolled 29 pts; (M13:F16); med...