Dose Escalation and Dose Expansion Study of CPO-100 in Patients With Advanced Solid Tumors

Inclusion Criteria - Parts A-1, A-2, and B:

1. Presence of a pathologically documented (histology or cytology) locally advanced or metastatic solid tumor cancer.
2. Patients has failed at least 2 lines of conventional systemic therapy or have no other standard of care therapies available for their cancer. Prostate cancer patients should have received adenosine triphosphate (ADT) alone,(GnRH agonist, GnRH antagonist, or surgical orchiectomy and a pathway targeted agent such as abiraterone, enzalutamide, etc (castration-resistant prostate cancer). M1 disease must be present (not just biochemical recurrence).
3. Male or female patients18 years of age or older.
4. ECOG (Eastern Cooperative Oncology Group) performance status (PS) of 0, 1 or 2
5. Having at least one measurable target lesion present and documented by RECIST 1.1 for each cancer other than prostate cancer. Patients with prostate cancer may be enrolled with non-measurable disease providing the patient with a prostate-specific antigen (PSA) increase that is ≥25% and ≥2 ng/mL above the nadir, which is confirmed by a second value ≥3 weeks later, or 2 or more new bone lesions on imaging.
6. Adequate major system function defined as:

   1. Bone marrow reserve:

      Absolute neutrophil count (ANC) ≥1.5 x109/L Platelet count ≥ 100 x109/L Hemoglobin ≥9 g/dL without transfusion (the patient needs to be transfusion independent)
   2. Hepatic function:

      Total bilirubin ≤ upper limit of normal (ULN) (unless the subject has Grade 1 bilirubin elevation due to Gilbert's disease or a similar syndrome involving slow conjugation of total bilirubin); And aspartate aminotransferase (AST) / serum glutamic oxaloacetic transaminase (SGOT) and/or alanine aminotransferase (ALT) / serum glutamic pyruvic transaminase (SGPT) ≤ 1.5 x ULN with alkaline phosphatase ≤2.5 x ULN.
   3. Renal function:

      Normal serum creatinine ≤1.5 mg/dL (133 μmol/L) OR calculated creatinine clearance ≥50 mL/min. (Cockcroft - Gault formula)
   4. Coagulation:

   Adequate coagulation parameters defined as International Normalization Ratio (INR) ≤2.
7. Adequate methods of contraception for female patients of reproductive potential during the study and for at least 6 months following last dose. Male patients with female partners of childbearing potential and women patients of childbearing potential are required to use two forms of acceptable contraception, including 1 barrier method, during their participation in the study and for at least 3 months following last dose. Male patients must also refrain from donating sperm during their participation in the study.
8. Life expectancy ≥3 months.
9. Willingness and ability to comply with study and follow-up procedures.
10. Ability to understand the nature of this study and give written informed consent.

Additional Inclusion Criteria for the dose expansion cohort - Part B

1. Pathologically confirmed (histology or cytology) of the following cancer types:

   1. Cohort 1: taxane naïve advanced/metastatic gastric cancer, lung cancer, head and neck cancer, or ovarian cancer;
   2. Cohort 2: taxane naïve advanced/metastatic breast cancer;
   3. Cohort 3: taxane naïve advanced/metastatic prostate cancer.
   4. Cohort 4: advanced/metastatic breast or ovarian cancer patients who have either progressed on a taxane or have developed progressive disease within 6 months of receiving a taxane;
2. With the exception of Cohort 4 above, taxane naïve patients must not have received taxane or taxane based therapies for their metastatic diseases. Patients who had suboptimal taxane exposure defined as having received less than 2 cycles of taxane or taxane based therapies due to intolerability for their metastatic diseases, patients who have received taxane or taxane based therapies for their neoadjuvant treatment or patients who have received taxane or taxane based therapies for their adjuvant treatment without disease progression during treatment are also considered taxane naïve, as long as they have not received taxane or taxane based therapies to treat the metastatic diseases.

Exclusion Criteria - Part A and B

1. Most recent chemotherapy ≤14 days or have residual NCI CTCAE greater than Grade 1 chemotherapy-related side effects, with the exception of alopecia.
2. Use of any experimental drug ≤28 days or 5 half-lives (whichever is shorter) prior to the first dose of CPO-100. For study drugs for which 5 half-lives is ≤28 days, a minimum of 14 days between termination of the study drug and administration of CPO-100 is required.
3. Wide field radiotherapy (including therapeutic radioisotopes such as strontium 89 and lutetium 177) administered ≤28 days or limited field radiation for palliation ≤7 days prior to starting study drug or has not recovered from side effects of such therapy.
4. Major surgical procedures ≤28 days of beginning study drug, or minor surgical procedures ≤7 days. No waiting required following port-a-cath placement.
5. Previously untreated brain metastases. Patients who have received radiation or surgery for brain metastases are eligible if therapy was completed at least 2 weeks previously and there is no evidence of central nervous system disease progression, and no requirement for chronic corticosteroid therapy.
6. Leptomeningeal metastases or spinal cord compression due to disease.
7. Known serious hypersensitivity reactions to docetaxel or life-threatening toxicity due to prior exposure to docetaxel
8. Pregnant or lactating.
9. Acute or chronic liver, renal, or pancreatic disease that in the opinion of the investigator would put the patient at unjustified increased risk by participating in this study or could interfere with the interpretation of the study results.
10. Other systemic disease that in the opinion of the investigator would put the patient at unjustified increased risk by participating in this study or could interfere with the interpretation of the study results.
11. Any of the following cardiac diseases currently or within the last 6 months:

    * Left ventricular ejection fraction (LVEF) \<50% as determined by multiple gated acquisition (MUGA) scan or echocardiogram (ECHO)
    * Corrected QT (QTc) interval \>470 ms (average of 3 tracings) on screening electrocardiogram (ECG)
    * Unstable angina pectoris
    * Congestive heart failure according to the New York Heart Association (NYHA) ≥ Grade 2)
    * Acute myocardial infarction
    * Conduction abnormality not controlled with pacemaker or medication
    * Significant ventricular or supraventricular arrhythmias. (Patients with chronic rate-controlled atrial fibrillation in the absence of other cardiac abnormalities are eligible.)
12. Inadequately controlled hypertension (ie, systolic blood pressure (SBP) \>180 mmHg or diastolic blood pressure (DBP) \>100 mmHg). Subjects with values above these levels must have their blood pressure (BP) controlled with medication prior to starting treatment.
13. Serious active infection at the time of treatment, or another serious underlying medical condition that that in the judgment of the investigator would impair the ability of the patient to receive protocol treatment.
14. HIV positive test within 8 weeks of screening. HIV positive patients with T-cell (CD4+) counts ≥350 cells/mL and not receiving treatment or does not plan to be treated with antiretroviral medication will be eligible for the study. Testing for seropositive status during screening will be at the discretion of the investigator in patients without previously reported results.
15. Active hepatitis B, or hepatitis C infection.

    * Patients will be tested for hepatitis C virus (HCV) and hepatitis B virus (HBV) at Screening.
    * Patients with hepatitis B (HepBsAg+) who have controlled infection (serum hepatitis B virus DNA level is below the limit of detection by PCR) may be enrolled into the study. Subjects with controlled infections must undergo periodic monitoring of HBV DNA per treating physician.
    * Patients with hepatitis C (HCV Ab+) who have controlled infection (undetectable HCV RNA by PCR either spontaneously or in response to a successful prior course of anti-HCV therapy) may be enrolled into the study. Patients with controlled infections must undergo periodic monitoring of HCV RNA per treating physician.
16. Presence of other active cancers, or history of treatment for invasive cancer ≤3 years. Patients with Stage I cancer who have received definitive local treatment and are considered unlikely to recur are eligible. All patients with previously treated in situ carcinoma (ie, non-invasive) are eligible, as are patients with history of non-melanoma skin cancer.
17. Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol.
18. Routine use of corticosteroids or erythrocyte-stimulating factors as well as prophylactic use of colony-stimulating factors.
19. Use of any strong CYP3A4 inhibitor or strong inducer drugs ≤28 days or 5 half-lives (whichever is shorter) prior to the first dose of CPO-100. For CYP3A4 inducer drugs for which 5 half-lives is ≤28 days, a minimum of 14 days between discontinuation of the drug and administration of CPO-100 is required.
20. Use of herbal preparations/medications including, but are not limited to: St. John's wort, kava, ephedra (ma huang), gingko biloba, dehydroepiandrosterone (DHEA), yohimbe, saw palmetto, and ginseng. A minimum of 14 days between discontinuation of the herbal preparation/medications and administration of CPO-100 is required.