Study of the Efficacy, Safety, and Pharmacokinetics of SM88 in Patients With Prostate Cancer

The purpose of this study is to evaluate the safety, pharmacokinetics, and efficacy of SM88 in patients with prostate cancer

This is an open-label, multi-center, dose-escalating, dose-expansion study of SM88 in patients with prostate cancer. This study includes 2 phases, a dose-escalation phase that includes PK evaluation, and a dose-expansion phase.

During the first stage, at up to 2 institutions, up to 2 cohorts of 1 to 6 patients each will be enrolled.

During the second stage, the dose selected for evaluation from the Phase 1b will be administered for a total of 30 evaluable patients (inclusive of those treated at the same dose during the dose selection phase) for 6 cycles or until unacceptable toxicity, disease progression, or until any of the treatment discontinuation criteria are met.

Eligibility Criteria:
Inclusion Criteria:

1. Male ≥18 years of age.
2. Histologically or cytologically confirmed prostate cancer (patients with neuroendocrine carcinoma of the prostate are excluded).
3. Documented PSA progression. Pre-enrollment PSA progression will be as defined by the PCWG3 criteria, e.g. 3 values, increasing, each \>7 days apart.
4. ECOG performance status ≤1
5. Life expectancy \>3 months, in the judgment of the investigator.
6. Adequate organ function defined as follows:

   1. Hematologic: Platelets ≥100 x 109 /L; Absolute Neutrophil Count (ANC) ≥1.5 x 109/L (without platelet transfusion or growth factors within the 7 days prior to the screening laboratory assessment)
   2. Hepatic: aspartate transaminase (AST)/alanine transaminase (ALT) ≤2.5 x upper limit of normal (ULN); total or conjugated bilirubin ≤1.5 x ULN
   3. Renal: serum creatinine ≤1.5 x ULN or creatinine clearance (CrCl) ≥60 mL/min as calculated by the Cockroft-Gault method
7. Coagulation: International normalized ratio (INR) ≤1.2
8. With or without one prior line of chemotherapy
9. With or without prior or current ADT or hormone based therapy (up to 2 lines total)
10. Cannot tolerate standard chemotherapy, hormone based therapy or ADT, or elects to opt out of standard therapies.
11. Patients who are on ADT prior to the study need not discontinue such therapy during the study, but the use of ADT during the study must be documented.
12. All acute toxic effects of any prior antitumor therapy resolved to Grade ≤1 before baseline, with the exception of alopecia (Grade 1 or 2 permitted) and neurotoxicity (Grade 1 or 2 permitted)
13. Male patients of fertile potential who engage in heterosexual intercourse with female partners of childbearing potential must agree to use highly effective contraception while enrolled in the study and for at least 6 months following the last dose of study drug. Highly effective birth control methods include the following (the patient should choose 2 to be used with their partner):

    1. Oral, injectable, or implanted hormonal contraceptives
    2. Condom with a spermicidal foam, gel, film, cream, or suppository
    3. Occlusive cap (diaphragm or cervical/vault cap) with a spermicidal foam, gel, film, cream, or suppository
    4. Intrauterine device
    5. Intrauterine system (for example, progestin-releasing coil)
    6. Vasectomized male (as determined by the investigator)
14. Able and willing to provide written informed consent to participate in this study

Exclusion Criteria:

1. PSA minimum starting value \<1 ng/mL at trial entry.
2. Metastatic disease as detected on bone scan, Computed Tomography (CT), Magnetic Resonance Imaging (MRI), or CT-positron emission tomography (PET) beyond the prostate or post-surgical prostate area.
3. Any screening laboratory, electrocardiogram (ECG), or other findings that, in the opinion of the investigator or the sponsor, indicate an unacceptable risk for the patient's participation in the study.
4. History or evidence of any clinically significant disorder, condition, or disease that, in the opinion of the investigator or medical monitor would pose a risk to the patient's safety or interfere with the study evaluations, procedures, or completion. Examples include intercurrent illness such as active uncontrolled infection, active or chronic bleeding event within 28 days of baseline, uncontrolled cardiac arrhythmia, or psychiatric illness/social situation that would limit compliance with study requirements.
5. History of a concurrent or second malignancy, except for adequately treated local basal cell or squamous cell carcinoma of the skin, superficial bladder cancer, adequately treated Stage 1 or 2 cancer currently in complete remission; or any other cancer that has been in complete remission for ≥5 years
6. Local therapy such as radiation or surgery within 8 weeks of study baseline.
7. Current use of a prohibited medication (see Section 8.5) or requires any of these medications during treatment phase
8. Major surgery, defined as any surgical procedure that involves general anesthesia and a significant incision (i.e., larger than that required for placement of central venous access, percutaneous feeding tube, or biopsy) within 28 days of the first dose of study drug
9. Minor surgical procedures within 7 days of baseline, or not yet recovered from prior surgery
10. Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of any of the components of SM88, e.g. cirrhosis
11. Known human immunodeficiency (HIV) virus infection
12. Hepatitis B surface antigen (HBsAg) positive
13. Hepatitis C virus (HCV) antibody positive
14. Have previously been enrolled in this study or any other study investigating SM88
15. History of any drug allergies or significant adverse reactions to any of the components of SM88.
16. Are currently enrolled in, or have discontinued within 30 days of screening, from a clinical trial involving an investigational product or non-approved use of a drug or device.