Dose escalation and DLTs
DLTs, hyperbilirubinemia, rash
PERIORBITAL EDEMA, HYPERBILIRUBINEMIA
In the Q2D dose escalation phase, cohorts of patients received tovorafenib doses of 20 mg, 40 mg, 80 mg, 135 mg, 200 mg and 280 mg Q2D in 22-day cycles, and 200 mg Q2D in 28-day cycles. DLTs occurred in cycle 1 in 2 patients in the 280 mg cohort; 1 patient had grade 3 periorbital edema and 1 had grade 3 maculo-papular rash. The MTD selected for the Q2D expansion cohorts was therefore 200 mg, to be administered over 28-day cycles. In the QW dose escalation phase, cohorts of patients received tovorafenib doses of 400 mg, 600 mg, and 800 mg, in 28-day cycles. DLTs occurred in cycle 1 in 2 patients in the 800 mg cohort; 1 patient had grade 3 hyperbilirubinemia and 1 had grade 3 rash. The MTD selected for the QW expansion cohort was therefore 600 mg to be administered over 28-day cycles.