A Phase I/II Study of BET and MEK inhibition in Advanced Uveal Melanoma

Uveal melanoma is a rare melanoma subtype associated with poor outcomes in the metastatic setting. Virtually all cases harbor activating mutations of GNAQ, GNA11, PLCB4 or CYSLTR2 which result in activation of the MAP kinase pathway, amongst others. In addition, epigenetic dysregulation is known to play a critical role in disease pathogenesis. Based on preclinical data showing that the combination of MEK inhibition and Bromodomain and Extra-terminal (BET) protein inhibition (an epigenetic regulator) is associated with synergistic anti-tumor activity, Dr. Khan will investigate the safety and efficacy of combined BET and MEK inhibition in a multi-center phase I/II clinical trial in patients with metastatic uveal melanoma. Translational components of this study will assess potential mechanisms of treatment response and resistance using tumor and blood samples from patients.