A Study of GSK2110183 in Subjects With Proteasome Inhibitor Refractory Multiple Myeloma

On Cycle 0, Day -3, three subjects will be enrolled to receive a single oral dose of 125mg GSK2110183. After the 72 hour PK sampling is completed, the subjects will continue the 125mg GSK2110183 dose daily for 21 day cycles. If none of the 3 subjects experience one of the DLTs listed in the protocol during Cycle 1, the dose will be escalated to 150mg GSK2110183 for the subject enrolled to Cohort 2. Alternately, if 1 subject reports a DLT, then 3 more subjects will be enrolled at the same dose. If 2 of 6 subjects report a DLT, then the MTD has been exceeded. Subjects will remain on study until they meet one of the Treatment Discontinuation Criteria.

For Cohort 2, on Cycle 0, Day -3, three subjects will be enrolled to receive a single oral dose of 150mg GSK2110183. After the 72 hour PK sampling is completed, the subjects will continue the 150mg GSK2110183 dose daily for 21 day cycles. If none of the 3 subjects experience one of the DLTs listed in the protocol during Cycle 1, the MTD will be determined unless the PK and Pharmacodynamic data indicates another dose level should be evaluated. Alternately, if 1 subject reports a DLT, then 3 more subjects will be enrolled at the same dose. If 2 of 6 subjects report a DLT, then the MTD has been exceeded. Subjects will remain on study until they meet one of the Treatment Discontinuation Criteria.

Following the completion of PK sampling and the determination of a Recommended Phase 2 Dose (RP2D) of GSK2110183 in Cohorts 1 and 2, subjects will be enrolled into Part 2, Stage 1 of the study. Twenty subjects will be enrolled in Stage 1. If no subject responds, the study will be stopped; otherwise, the study will continue enrollment of Stage 2.

Twenty subjects will be enrolled in Part 2, Stage 2. If 4 or fewer of the 40 subjects (Stages 1 and 2) respond, the study will not be deemed as a success for GSK2110183 monotherapy. However, those subjects meeting the criteria for progression (as defined by IMWC Panel 1) who also meet the additional eligibility criteria for salvage therapy may proceed to GSK2110183 + bortezomib salvage therapy. GSK2110183 + bortezomib salvage therapy will be continued until one of the Treatment Discontinuation Criteria is met