A Phase I/II Open-Label, Dose Escalation Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics, and Clinical Activity of GSK525762 in Subjects With NUT Midline Carcinoma (NMC) and Other Cancers

This study is divided into two parts; Part 1 of the study is a dose escalation phase to
select the recommended dose for Part 2 based on the safety, pharmacokinetic, and
pharmacodynamic profiles observed after oral administration of GSK525762 in the following
subjects: NMC, small cell lung cancer (SCLC), non-small cell lung cancer (NSCLC), colorectal
cancer (CRC), neuroblastoma (NB), castration resistant prostate cancer (CRPC), triple
negative breast cancer (TNBC), estrogen receptor positive (ER positive) breast cancer, and
MYCN driven solid tumor subjects. Part 2 of the study will explore the safety, tolerability,
pharmacokinetics, pharmacodynamics, and clinical activity of the recommended dose from Part 1
in cohorts comprised of NMC, small cell lung cancer (SCLC), castration resistant prostate
cancer (CRPC), triple negative breast cancer (TNBC), and estrogen receptor positive (ER
positive) breast cancer subjects. Approximately 60 subjects will be enrolled in the Part 1
and approximately 150 subjects will be enrolled in Part 2. A sub-study will be opened in Part
1 to approximately 10-12 subjects in the United States to investigate the relative
bioavailability of the besylate tablet compared to the amorphous free-base tablet at the
maximum tolerated dose (MTD) or recommended phase 2 dosing (RP2D), the effect of high-fat
high-calorie meal on the bioavailability of the besylate tablet at the MTD or RP2D and the
dose proportionality of 2 doses of GSK525762 administered as besylate tablet.