Phase 1/2a Trial Of Intravenous Bal101553, A Novel Tumor Checkpoint Controller (Tcc), In Advanced Solid Tumors.

2525Background: BAL101553 (prodrug of BAL27862) is a small molecule TCC that binds microtubules and promotes tumor cell death through activation of the mitotic checkpoint. Antiproliferative effects appear driven by AUC; vascular disruption by Cmax . In a NSCLC xenograft mouse model, dose-dependent vascular disruption with reduction of tumor perfusion was observed. Methods: Patients (pts) with advanced solid tumors who failed standard therapy, received 2-h intravenous (IV) BAL101553 on days 1, 8 and 15 of each 28-day cycle. The Phase 1 (P1) part of the study used an accelerated 3+3 dose-escalation design to determine the maximum tolerated dose (MTD). In Phase 2a (P2a), pts were randomized to assess whether MTD or sub-MTD doses provide better anti-tumor activity. Adverse events were assessed by CTCAEv4 grade (G); tumor response by RECIST 1.1 every 2 cycles. Assessments included PK, tumor biopsies, functional imaging, and analysis of circulating tumor, endothelial and endothelial progenitor cells (CTCs, CECs...