Phase 1/2a study of once daily oral BAL101553, a novel tumor checkpoint controller (TCC), in adult patients with advanced solid tumors.

2530Background: BAL101553 is the prodrug of BAL27862, a small molecule TCC that binds microtubules and promotes tumor cell death by activation of the spindle assembly checkpoint. In a study of BAL101553 administered as 2-h infusions on Days 1, 8 and 15 of a 28-day cycle (NCT01397929, Lopez et al. JCO 34, 2016; abstr 2525), vascular toxicities (troponin increases/ECG changes suggestive of microvascular myocardial injury and hypertension) were observed and appeared to be Cmax related. Nonclinical models indicate that the antiproliferative effects of BAL27862 are AUC driven; this trial was designed to determine whether oral once-daily (QD) administration of BAL101553 reduces Cmax-related toxicity and increases the AUC at the Recommended Phase 2 Dose (RP2D) (NCT02490800, Kristeleit et al. JCO 35, 2017; abstr 2532). Methods: Adult patients with advanced solid tumors received QD oral BAL101553 (28-day cycles) in a 3+3 dose-escalation design to determine the maximum tolerated dose (MTD). Adverse events (AEs) wer...