ProSTAR: A Phase 1b/2 Study of CPI-1205, a Small Molecule Inhibitor of EZH2, Combined with Enzalutamide or Abiraterone/Prednisone in Patients with Metastatic Castration Resistant Prostate Cancer

This is a two-arm, open label Phase 1b/2 study with an oral administration of CPI-1205 in
combination with either enzalutamide or abiraterone/prednisone in male patients with
metastatic Castration Resistant Prostate Cancer. This study is designed to determine the
maximum tolerated dose (MTD) and recommended Phase II dose (RP2D) based on safety,
tolerability, pharmacokinetic, and efficacy profiles of CPI-1205 in combination with either
enzalutamide or abiraterone/prednisone.

Following determination of MTD and RP2D will proceed to phase 2. Patients in phase 2 will
receive CPI-1205 at the RP2D in combination with either enzalutamide or
abiraterone/prednisone vs either enzalutamide or abiraterone/prednisone as a control arm.

Inclusion Criteria:

- Adults (Age ≥ 18 years)

- Eastern Cooperative Oncology Group (ECOG) performance status 0-1

- Life expectancy of at least 12 weeks

- Histologically or cytologically confirmed adenocarcinoma of the prostate

- Progressive disease in the setting of medical or surgical castration (i.e. CRPC)

- Documented metastatic disease

- Must have undergone bilateral orchiectomy (surgical castration) or be willing to
continue gonadotropin-releasing hormone (GnRH) analog or antagonist (medical
castration)

- Serum testosterone <50 ng/dL

- Receipt of prior line of second generation androgen inhibitor

- Demonstrate adequate organ function as defined below:

- Absolute Neutrophil Count (ANC) ≥ 1,000/μL

- Platelet Count ≥ 100,000/μL

- Hemoglobin (Hgb) ≥ 8 g/dL

- Serum creatinine ≤ 2 × upper limit of normal (ULN) OR

- Creatinine clearance (CrCl) ≥ 40 mL/min as estimated by the Cockcroft and Gault
formula1 in subjects with creatinine > 2 X ULN

- Bilirubin ≤ 1.5 × ULN unless evidence of Gilbert's disease in which case < 3 x
ULN

- Aspartate aminotransferase (AST) ≤ 2.5 × ULN without liver metastases; must be ≤
5 × ULN with liver metastases

- Alanine aminotransferase (ALT) ≤ 2.5 × ULN without liver metastases; must be ≤ 5
× ULN with liver metastases

Exclusion Criteria:

- Known symptomatic brain metastases (NOTE: patients with treated epidural disease are
allowed)

- Treatment with any of the following for prostate cancer within the indicated timeframe
prior to day 1 of treatment:

1. First generation: AR antagonists (e.g., bicalutamide, nilutamide, flutamide)
within 4 weeks

2. 5 alpha reductase inhibitors, ketoconazole, estrogens (including
diethylstilbesterol [DES]), or progesterones within 2 weeks

3. Chemotherapy within 3 weeks

4. Biologic therapy within 4 weeks

5. Investigational therapy within 3 weeks (or within a time interval less than at
least 5 half-lives of the investigational agent [if known], whichever is longer).

6. Immunotherapy within 4 weeks

7. Prior radionuclide therapy within 4 weeks