Zelboraf vemurafenib: Phase I data

Data from 6 metastatic melanoma patients with V600E BRAF mutations in the first cohort of a Phase I trial showed that twice-daily oral 960 mg Zelboraf vemurafenib plus 3 mg/kg Yervoy ipilimumab every 3 weeks - the full approved doses for each drug - led to dose-limiting toxicities (DLTs) of grade 3 elevated aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels in 4 patients. Data from the first 4 patients in the second cohort showed that twice-daily 720 mg Zelboraf plus 3 mg/kg Yervoy every 3 weeks led to grade 3 elevated AST and ALT levels in 2 patients and grade 2 elevated aminotransferase levels in 1 patient. Additionally, 1 patient in each cohort had grade 2 or 3 elevated bilirubin levels with concomitant grade 3 elevations in aminotransferase levels. The trial was closed to further patient enrollment due to the toxic liver effects observed. Data were published in the New England Journal of Medicine. ...