Efficacy studies in xenograft models

For efficacy studies, xenograft tumor samples were cleaned and then minced, mixed with matrigel and implanted into a subcutaneous flank of female NSG mice to generate xenografts. Tumor-bearing animals were randomized to groups of five when tumors reached approximately 100 mm³ volume so that averages of tumor volume within and between groups were similar. Treatment was initiated with vehicle, cabozantinib (at 10, 25, 30, 50 or 100 mg/kg QD) or RXDX-105 (30 mg/kg BID). Cabozantinib was reconstituted in a vehicle consisting of 30% polypropylene glycol, 5% Tween-80 and 65% D5W (dextrose 5% water) and RXDX-105 was resuspended in 15% captisol. Both compounds were administered by oral gavage. Tumor size and body weight were measured twice weekly, and tumor volume was calculated using the formula: length×width2×0.52.