Study of Drug 1 (Enzalutamide) Plus Drug 2 (Relacorilant) for Patients With Prostate Cancer

The study is an open-label Phase 1 study of the combination of relacorilant with enzalutamide
in patients with metastatic castration resistant prostate cancer (mCRPC). Patients will be
enrolled in 6 patient cohorts with a 6+3 design and a 28 day DLT period. Doses of
relacorilant, enzalutamide will be adjusted based on safety and pharmacokinetics (PK). Once a
safe dose with appropriate drug levels (PK) has been established, the cohort will be expanded
to a total of 12 patients to refine safety and PK at the recommended phase II dose (RP2D).

Inclusion Criteria:

1. Histologically or cytologically confirmed prostate cancer with documented metastatic
disease

2. Evidence of castrate testosterone level <50ng/dl (or surgical castration)

3. Evidence of disease progression:

- 2 or more new lesions on bone scan or

- Progressive disease on CT/MRI according to Response Evaluation Criteria in Solid
Tumors 1.1 criteria or

- Rising Prostate Specific Antigen (PSA): PSA evidence for progressive prostate
cancer consists of a minimum PSA level of at least 2 ng/ml, which has
subsequently risen on at least 2 successive occasions, at least 2 weeks apart.

4. Prior treatment with at least one line of potent androgen receptor signaling inhibitor
(e.g. abiraterone, enzalutamide, apalutamide) in either castration-sensitive or
castration-resistant setting.

5. Any prior therapy for castrate disease is acceptable except prior GR antagonist
treatment (e.g. mifepristone or relacorilant).

6. Any other radiotherapy or radionuclide require 28-day washout prior to first dose of
study drug.

7. Denosumab or zoledronic acid are allowed.

8. ECOG performance status ≤ 2.

9. Patients must have normal hepatic function as defined below:

- Total bilirubin
- AST(SGOT)/ALT(SGPT)
- Albumin >/=3.0 g/dL

10. Patients must have normal bone marrow function as defined below:

- Platelet count (plt) >/= 80,000 /microliter

- Hemoglobin (Hgb) >/= 9 g/dL

- Absolute neutrophil count (ANC) >/= 1500

11. Patients must have normal renal function as defined below:

- GFR >/= 30 mL/min

12. Ability to understand and the willingness to sign a written informed consent document.

13. Patients with active Diabetes Mellitus on glucose lowering medications are eligible
provided they agree to and are able to self-monitor daily blood glucose levels due to
potential risk of lowering glucose levels on relacorilant.

14. Male patient and his female partner who is of childbearing potential must use 2
acceptable methods of birth control (one of which must include a condom as a barrier
method of contraception) starting at screening and continuing throughout the study
period and for 3 months after final study drug administration. Two acceptable methods
of birth control thus include the following:

- Condom (barrier method of contraception); AND

- One of the following is required:

1. Established use of oral, or injected or implanted hormonal method of
contraception by the female partner;

2. Placement of an intrauterine device (IUD) or intrauterine system (IUS) by
the female partner;

3. Additional barrier method: Occlusive cap (diaphragm or cervical/vault caps)
with spermicidal foam/gel/film/cream/suppository by the female partner;

4. Tubal ligation in the female partner;

5. Vasectomy or other procedure resulting in infertility (e.g., bilateral
orchiectomy), for more than 6 months.

Exclusion Criteria:

1. Therapy with other hormonal therapy, including any dose of megestrol acetate (Megace),
finasteride (Proscar), dutasteride (Avodart), or any herbal product known to decrease
PSA levels (e.g., saw palmetto and PC-SPES), or any systemic corticosteroid within 2
weeks prior to first dose of study drug.

a.Patients who have been on systemic corticosteroids with prednisone equivalent of
10mg or greater for greater than 3 months immediately prior to participation in this
study must have documented ability to tolerate cessation of corticosteroids prior to
enrollment.

2. Inability to swallow capsules or known gastrointestinal malabsorption.

3. Evidence of visceral disease on imaging in a patient who is an appropriate candidate
for cytotoxic chemotherapy (docetaxel or cabazitaxel).

4. History of other malignancies, with the exception of: adequately treated non-melanoma
skin cancer, adequately treated superficial bladder cancer, stage 1 or 2 malignancies
who are without evidence of disease, or other cancers curatively treated with no
evidence of disease for > 5 years from enrollment.

5. Blood pressure that is not controlled despite > 2 oral agents (SBP >160 and DBP >90
documented during the screening period with no subsequent blood pressure readings
>160/100).

6. History of seizure disorder or active use of anticonvulsants. Medications used to
treat neuropathic pain such as gabapentin or pregabalin are allowed.

7. Documented history of or current brain metastases due to seizure risk

8. Serious intercurrent infections or non-malignant medical illnesses that are
uncontrolled.

9. Active psychiatric illness/social situations that would limit compliance with protocol
requirements.

10. NYHA class II, NYHA class III, or IV congestive heart failure (any symptomatic heart
failure).

11. Concurrent therapy with strong inhibitors or inducers of CYP3A4 or CYP2C8 (See Section
9.12below for list of strong inhibitor or inducers) due to concerning possible
drug-drug interactions

12. Presence of concurrent medical conditions requiring systemic glucocorticoids for
immunosuppression (e.g. Autoimmune diseases, organ transplantation) that is active and
has required glucocorticoids in the last 6 months.