A Phase I Study of SOR-C13 in Patients With Advanced Solid Tumors

Inclusion Criteria: To be eligible for this trial, patients must meet all of the following eligibilitycriteria.

1. Subjects with a histologic diagnosis of solid tumor cancers of epithelial origin (metastatic epithelial ovarian, pancreatic and prostate cancers are preferred sincethese tumor types have TRPV6 overexpression).
2. Subjects with advanced refractory cancer for which standard curative or palliativemeasures do not exist or are no longer effective. There is no limitation on the numberor types of prior therapy.
3. Patients must have measurable or evaluable disease, as defined by Response EvaluationCriteria in Solid Tumors 1.1 (RECIST1.1).
4. Men or women aged ≥ 18 years.
5. Women of child-bearing potential (who are not postmenopausal for at least one year orare not surgically sterile) and men must agree to use adequate contraception (e.g.,hormonal, barrier device, or abstinence) prior to study entry, for the duration ofstudy participation, and for 30 days after the last dose the study agents.
6. Patients must have an ECOG performance status of 0 to 1.
7. Patients must have adequate organ functions as defined below:

• Neutrophils ≥ 1,500 /L
• Platelets ≥ 100,000 /L
• Total bilirubin ≤ 1.5 x ULN (upper limit of normal) (except patients withGilbert's syndrome, who must have a total bilirubin ≤ 3.0 mg/dL)
• ALT ≤ 2.5 x ULN or ≤ 5 x ULN if liver metastases persist
• Serum creatinine ≤ 1.5 x ULN or calculated creatinine clearance ≥ 45 mL/minute bythe Cockcroft-Gault method
• Albumin ≥ 3.0 g/dL (≥30 g/L)
• INR (international normalized ratio) ≤1.4

8. Patients should be able to read and fully understand the requirements of the trial, bewilling to comply with all trial visits and assessments, and be willing and able tosign an IRB-approved written informed consent document.
9. Subjects must have recovered from major infections and/or surgical procedures and, inthe opinion of the investigator, not have a significant active concurrent medicalillness precluding protocol treatment.
10. Patients agree to provide archival tissue block or 10 formalin-fixed paraffin-embedded (FFPE) slides paraffin for use in pharmacodynamics correlative studies.

Exclusion Criteria: Patients who meet any of the following criteria will be not eligible for the study.

1. Uncontrolled intercurrent illness including, but not limited to, ongoing or activeinfection requiring intravenous antibiotics, symptomatic congestive heart failure (NYHA Class III or IV), or history of myocardial infarction, unstable angina, strokeor transient ischemic attack within 6 months prior to study enrollment.
2. History of clinically significant allergic reactions to the study drugs or theiranalogs, or any component of the products.
3. Any treatment specific for systemic tumor control within 3 weeks prior to theinitiation of the study drugs; or within 2 weeks if cytotoxic agents were given weekly (within 6 weeks for nitrosoureas or mitomycin C), or within 5 half-lives for targetedagents with half-lives and pharmacodynamic effects lasting less than 4 days, orfailure to recover from toxic effects of any therapy prior to the study drugtreatment.
4. Patients who have not recovered from major surgical procedure, or significanttraumatic injury (i.e., still need additional medical care for these issues).
5. History of any of the following cardiovascular events or conditions within the past 6months prior to enrolment: myocardial infarction, unstable angina, cerebrovascularaccident or transient ischemic attack, New York Heart Association Class ≥ II chronicheart failure, significant arrhythmia*; QTcF interval >430 msec or use of drugs thatprolong the QT interval at screening; family history of long QT syndrome. *Significant arrhythmias are defined as symptoms of syncope or severe palpitations (palpitations requiring referral to cardiac monitoring), or ECG findings ofsupraventricular tachycardia (including atrial fibrillation or atrial flutter) orventricular tachycardia (including ventricular fibrillation) or ventricular ectopy (ventricular premature depolarization)
6. Clinically significant and uncontrolled major medical condition(s) that places thesubject at an unacceptably high risk for toxicities. These include, but are notlimited to: active infections, symptomatic pulmonary disease, inadequate pulmonaryfunction, seizure disorder, or psychiatric illness.
7. Current use of more than one antihypertensive medication.
8. For patients receiving antihypertensive medication: systolic blood pressure <120 mm Hgand/or diastolic blood pressure <70 mm Hg at screening.
9. Major surgical procedure within 4 weeks prior to enrolment.
10. Lactating or pregnant female.
11. Females of childbearing potential and males not using adequate birth control.
12. Current treatment or treatment within 4 weeks of screening with bisphosphonates.
13. Hypocalcemia at screening.
14. History of acute pancreatitis within 6 months prior to screening.
15. Known hypoparathyroidism, pseudohypoparathyroidism, or vitamin D deficiency, orclinical evidence of other conditions known to associated with hypocalcemia, includinghypoalbuminemia, hyperphosphatemia, hypomagnesemia.
16. Current treatment or treatment within 4 weeks of screening with drugs known to reduceserum calcium levels, including: bisphosphonates, antiepileptic drugs, cinacalcet,macrolide antibiotics (such as erythromycin, azithromycin), large doses ofcorticosteroids (>20 mg/day of prednisone or equivalent), or any IV use ofcorticosteroids. In addition, long-term use (defined as ongoing use for ≥4 weeks) ofcorticosteroids within 8 weeks of screening is prohibited.
17. Symptomatic and uncontrolled metastasis to the central nervous system orleptomeningeal or lymphangitic carcinomatosis.
18. Grade 2 or higher peripheral neuropathy.
19. Human immunodeficiency virus requiring HAART treatment due to unknown drug-druginteractions or known active hepatitis B or C.