Dataset from A Phase I, Open-label, Dose-finding Study of GSK2636771 Administered in Combination With Enzalutamide (Xtandi^TM ) in Male Subjects With Metastatic Castration-Resistant Prostate Cancer (mCRPC)

This Phase I, open-label, dose-finding, multicenter study is designed to determine the
recommended Phase II dose (RP2D) for the combination of an orally administered
Phosphatidylinositol-4,5-bisphosphate 3-kinase beta (PI3K-beta) inhibitor (GSK2636771) with
enzalutamide. Subjects with phosphatase and tensin homolog (PTEN)-deficient metastatic
castration-resistant prostate cancer (mCRPC) who are receiving a stable dose of enzalutamide
with a recently demonstrated progression (either by RECIST [Response Evaluation Criteria In
Solid Tumors] version 1.1, prostate-specific antigen [PSA] progression, and/or progression in
bone) per the Prostate Cancer Working Group 2 (PCWG2) criteria will be enrolled. Eligible
subjects will be enrolled in the Dose-Escalation Phase to determine the maximum tolerated
dose (MTD) of the combination therapy using a modified 3+3 dose escalation procedure. The
safety, pharmacokinetics (PK) and clinical efficacy will also be assessed to guide the
selection of the RP2D. The starting dose will be GSK2636771 300 mg once daily in combination
with the recommended dose (160 milligram [mg] once daily) of oral enzalutamide. Once the RP2D
has been established, additional subjects will be enrolled in the Dose Expansion Phase to
further evaluate the safety, PK and preliminary clinical activity. Safety assessments will be
performed throughout the study including physical examinations, vital signs, clinical
laboratory tests, 12 lead electrocardiograms and monitoring of adverse events. Blood samples
will be collected for pharmacokinetic analysis. Subjects will continue treatment until an
unacceptable toxicity, disease progression, withdrawal of consent or death occurs. A
post-treatment follow-up visit will be performed within 30 days of the last dose of study
treatment. Xtandi is a registered trademark of Astellas Pharma Inc