A Phase I Study to Investigate the Safety, Pharmacokinetics, and Pharmacodynamics of GSK2118436 in Subjects With Solid Tumors

BRF112680 is a first-time-in-human study to establish the recommended dose and schedule of
the orally administered GSK2118436. The recommended dose and regimen will be selected based
on the safety, pharmacokinetic, and pharmacodynamic profiles observed after the treatment of
subjects with solid tumors. This is a two-part study. Part 1 will identify the recommended
Part 2 dose using a dose-escalation procedure. Escalation may proceed until either a
maximum tolerated dose is established, or the toxicokinetic safety limit is reached. The
recommended Part 2 dose will be expanded to up to 12 patients. Part 2 will explore further
the safety, tolerability, and clinical activity of GSK2118436 in subjects with BRAF
mutation-positive tumors. In addition, the effect of GSK2118436 on midazolam will be
assessed in a subset of patients in Part 2. Biologically active doses will be identified by
measurement of pharmacodynamic markers in tumor tissue and blood across a range of doses and
these doses may be explored in Part 2.