Phase Ib of Abiraterone Acetate Plus BEZ235 or BKM120 in Castration-resistant Prostate Cancer (CRPC) Patients

A dose-escalation part will first determine the maximum tolerated dose (MTD) and/or
recomended dose for expansion (RDE) of abiraterone acetate in combination with BEZ235 and
abiraterone acetate in combination with BKM120 in CRPC patients with abiraterone acetate
failure.

Subsequently, the MTD and/or RDE of each combination will be investigated in two expansion
treatment groups of CRPC patients who have failed abiraterone acetate therapy.

Inclusion Criteria:

- Adult males ≥ 18 years old

- Eastern Cooperative Oncology Group Performance Status ≤ 2

- Patient must have a castrate level of testosterone (<= 50 ng/dL or 1.7 nmol/L). (
Castrate status must be maintained by continued GnRH analogues unless patient has
undergone surgical orchiectomy).

- Histologically or cytologically confirmed diagnosis of advanced or metastatic
prostate cancer.

- Advanced or metastatic castration-resistant prostate cancer progression after
abiraterone acetate failure

- Patients should have no more than 2 lines of prior chemotherapies including cytotoxic
agents

- Discontinuation of all anti-androgen, anti-neoplastic or investigational treatment >=
4 weeks (6 weeks for bicalutamide).

Exclusion Criteria:

- Previous treatment with PI3K pathway inhibitors (e.g. PI3K, AKT, mTOR inhibitor),
ketoconazole, CYP17 inhibitors (exception of AA), or enzalutamide.

- Patient has active uncontrolled or symptomatic CNS metastases

- Inadequately controlled hypertension (e.g. systolic blood pressure >=160 mmHg or
diastolic blood pressure >=95 mmHg)

- Patient has a QTcF > 480 msec on the screening ECG (using the QTcF formula), has a
short/long QT syndrome, or history of QT prolongation/Torsades de Pointes

- Patient has impairment of gastrointestinal (GI) function or GI disease that may
significantly alter the absorption of study drugs

- Patient has a medically documented history of or active major depressive episode,
bipolar disorder (I or II), obsessive-compulsive disorder, schizophrenia, a history
of suicidal attempt or ideation, or homicidal ideation (e.g. risk of doing harm to
self or others)

- Patients who experienced dose reductions and/or treatment interruptions due to
abiraterone acetate related toxicities (i.e. serious AEs, AEs, liver toxicities
during abiraterone acetate treatment