A Phase 1 Study To Assess The Safety, Pharmacokinetics (Pk), Pharmacodynamics (Pd) And Antitumor Activities Of Daily Oral Bal101553, A Novel Tumor Checkpoint Controller (Tcc) In Adult Patients With Advanced Solid Tumors.

TPS2594Background: BAL101553 is the pro-drug of BAL27862, a novel small molecule TCC that promotes tumor cell death by modulating the spindle assembly checkpoint (SAC). In a completed Phase 1 (P1) study, pre- and post-treatment tumor biopsies revealed antiproliferative and vascular disrupting PD effects with BAL101553 administered as a 2-hour intravenous infusion1. The time profile of transient blood pressure elevations linked the vascular effects of the drug to Cmax, while preclinical data suggest that effects on tumor cell proliferation are AUC-mediated; vascular toxicity was dose-limiting. Given this, dosing strategies that optimize the PK/PD profile, particularly those that minimize the Cmax, may allow higher doses and/or exposures of BAL27862 to be tolerated. Preclinical data with oral BAL101553 in various animal models, including colorectal, lung cancer and glioblastoma xenograft models, suggest excellent bioavailability and antitumor efficacy. Methods: This is an ongoing multicenter, open-label, Ph...