3.2 Dose-Limiting Toxicities and Dose Determination
At dose level 1, three of six patients developed first cycle DLT: grade
3 epistaxis; prolonged grade 2 increased alanine aminotransferase (ALT);
prolonged grade 2 thrombocytopenia that delayed the start of the second
cycle. Therefore, dose level 1 was considered not tolerable. Two of
three DLTs were non-hematologic DLTs and dose level -1B with interrupted
cabozantinib dosing was evaluated. Six patients were enrolled on dose
level -1B, with one first cycle DLT (grade 3 pneumothorax) observed.
This established dose level -1B as the MTD and RP2D.