Fig. 4.

Combined treatment of NSCLC tumor xenografts with TVB-3166 and a taxane (paclitaxel or docetaxel) inhibits tumor growth synergistically compared to single agent activity. A minimum of 10 mice per treatment group was used in all studies. (A) CALU6 NSCLC adenocarcinoma cell line. (B) A549 NSCLC adenocarcinoma cell line. (C) CTG-0165_P + 6 NSCLC adenocarcinoma patient-derived tumor. TVB-3166 was dosed once daily by oral gavage at 60 mg/kg. Paclitaxel was dosed once every 4 days by intravenous administration at 10 mg/kg. Docetaxel was dosed once every 7 days by intravenous administration at 8 or 6 mg/kg. In groups dosed with both TVB-3166 (60 mg/kg) and paclitaxel (10 mg/kg) or docetaxel (8 or 6 mg/kg), TVB-3166 was administered 2 h before taxane administration. Animals were randomized according to tumor size and drug treatment was started when the mean tumor size was 150–200 mm³. Tumors and blood samples were harvested 2 h after the last dose. TVB-3166 and paclitaxel plasma and tumor drug concentrations were determined by mass spectrometry. The in-life phase for the CALU-6 (A) and A549 (B) studies was performed at Crown Biosciences (Santa Clara, CA; Beijing, China). The in-life phase for the CTG-0165_P + 6 study (C) was performed at Champions Oncology (Baltimore, MD).