Phase I study of BAY 73–4506, a multikinase inhibitor, administered for 21 days on/7 days off in patients with advanced solid tumors

3593 Background: BAY 73–4506 is a multikinase inhibitor targeting both the tumor and its vasculature. BAY 73–4506 inhibits VEGFR-2 and -3, and tumor cell signaling kinases (RET, KIT, PDGFR, and Raf). This drug shows potent, oral activity in a wide variety of preclinical xenograft models. Methods: This phase I dose-escalation trial investigated the safety, pharmacokinetic (PK), and pharmacodynamic (PD) profile of BAY 73–4506 given orally in 21 days on/7 days off cycles, until discontinuation due to toxicity or tumor progression. PK was assessed on days 1 and 21 of cycle 1. PD markers included dynamic contrast-enhanced MRI (DCE-MRI) and circulating sVEGFR-2 and VEGF levels assessed at each cycle. Tumor response was evaluated per RECIST criteria. Results: 22 patients (pts) with documented progressive disease were enrolled at doses of 10 mg to 120 mg once daily. Tumor types included CRC (27%), RCC (18%) and pancreatic cancer (14%). Pts had received a median of 3 prior therapies, including anti-VEGF agents in ...