SHIP (Selinexor in Hormone Insensitive Prostate Cancer)

This is a Phase 2, open-label study to explore the effect of selinexor (KPT-330) therapy in
patients with metastatic castration-resistant prostate cancer (mCRPC). Approximately 50
patients are planned for enrollment. Patients will receive an oral dose of selinexor on one
of three dosing schedules.

Inclusion Criteria:

- Histologically proven adenocarcinoma of the prostate with evidence for skeletal
metastases on bone scan and/or CT scan.

- Must have received at lease one agent known to impact survival (abiraterone,
enzalutamide, ect.)

- Eastern Cooperative Oncology Group (ECOG) ≤ 2 or a Karnofsky Performance Status (KPS)
≥ 60%.

- Serum testosterone levels < 50ng/ml

- Ongoing gonadal androgen deprivation therapy with LHRH analogues or orchiectomy.
Patients, who have not had an orchiectomy, must be maintained on standard dosing of
LHRH analogue therapy at appropriate frequency for the duration of the study

- Progression of disease despite androgen ablation shown by objective, documented
evidence of disease progression (excluding PSA).

- Discontinuation of any glucocorticoids prescribed to specifically treat prostate
cancer (e.g., as a secondary hormonal manipulation) > 4 weeks prior to receiving first
dose of study drug. Glucocorticoids prescribed for a chronic non-cancer-related
illness (e.g., asthma or COPD) that is well controlled with medical management are
permissible to an equivalent of ≤ 10 mg prednisone daily.

Exclusion Criteria:

- Histologic variants other than adenocarcinoma in the primary tumor

- Patients who require or may be expected to require urgent treatment with docetaxel
during the study (e.g., patients with visceral metastases).

- Therapy with other hormonal therapy, including any herbal product known to decrease
PSA levels (e.g., Saw Palmetto and PC-SPES) within 4 weeks prior to receiving first
dose of study drug.

- Therapy with samarium-153, strontium-89, or radium-223 within 8 weeks prior to first
dose of study drug.

- Prior external beam radiation therapy completed < 3 weeks or single fraction of
palliative radiotherapy within 14 days prior to first dose of study drug.

- Any "currently active" second malignancy, other than non-melanoma skin cancer.
Patients are not considered to have a "currently active" malignancy, if they have
completed therapy and are considered by their physician to be at least less than 30%
risk of relapse over next 3 months.

- Active or uncontrolled autoimmune disease that may require corticosteroid therapy
during study

- Severely compromised immunological state, including known human immunodeficiency virus
(HIV)

- Known acute or chronic hepatitis B or C

- Chemotherapy and other investigational therapies (targeted or immunotherapy) will
require a 3-week washout period before treatment initiation