Discussion
diarrhea, toxicity, rash, cardiac disorders, Toxicity, thoracic and mediastinal disorders
FACE EDEMA, EYE DISORDERS, PERIPHERAL EDEMA, CARDIAC DISORDERS
Our findings showed that HL-085 was well tolerated, with the most common AEs of skin-related AEs and increased CK were manageable. No DLT occurred in the dose- escalation phase and MTD was therefore not reached. Anti-tumor activity were first observed in the 4 mg dose cohort with PR first observed at the 9 mg dose, suggesting dose-dependent anti-tumor activity of HL-085. Toxicity of HL-085 increased with dose (respiratory, thoracic and mediastinal disorders, cardiac disorders and eye disorders requiring discontinuation of HL-085 in the 15 and 18 mg dose cohorts). Based on the absence of severe toxicity and promising evidence of efficacy in the dose-escalation phase, 12 mg BID was identified as the RP2D for HL-085 and was selected for dose expansion.In this study, the most common AEs included rash, increased CK, increased AST, face edema, increase ALT, peripheral edema, and diarrhea. The AEs profile was similar to those seen with other MEK inhibitors in previous trials [As shown in the spider plot (Fig. Syeda et al. [