Inclusion Criteria:
1. Patients must have histologically (or cytologically) confirmed diagnosis of solid tumor, refractory after standard therapy for the disease or for which conventional systemic therapy is not reliably effective or no effective therapy is available. Note: For expansion cohorts patients must have histologically (or cytologically) confirmed diagnosis of gastroesophageal cancer, pancreatic cancer, or cholangiocarcinoma that has relapsed or is refractory to standard therapy.
2. Aged ≥ 18 years.
3. ECOG Performance Status of 0 or 1.
4. Adequate clinical laboratory values defined as:
1. absolute neutrophil count ≥ 1.5 x 10⁹/L
2. platelets ≥ 100 x 10⁹/L
3. hemoglobin ≥ 9.0 g/dL (transfusions permissible)
4. plasma creatinine ≤ 1.5 x upper limit of normal (ULN) for the institution or calculated clearance ≥ 60 mL/min (Cockcroft-Gault formula)
5. total bilirubin ≤ 1.5 x ULN
6. alanine transaminase (ALT) and aspartate transaminase (AST) \< 2.5 x ULN (\<5 x ULN if documented hepatic metastases)
7. prothrombin time (PT) ≤1.2 x ULN, partial thromboplastin time (PTT) ≤ 1.2 ULN, and international normalized ratio (INR) ≤ 1.5
5. Absence of uncontrolled intercurrent illnesses, including uncontrolled infections, cardiac conditions, uncontrolled diabetes mellitus, or other organ dysfunctions.
6. Patients may have measurable or non-measurable disease as defined by RECIST 1.1.
7. Signed Informed-consent prior to the start of any study specific procedures.
8. Women of child-bearing potential must have a negative serum or urine pregnancy test. Male and female patients must agree to use acceptable contraceptive methods for the duration of the study and for at least one month after the last drug administration.
Exclusion Criteria:
1. Patients will be excluded if they have received previous chemotherapy, immunotherapy, radiotherapy or any other investigational therapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) or 5 half-lives for targeted therapies prior to this study entry.
2. Have not recovered from adverse events (must be Grade ≤1) due to agents administered more than 4 weeks earlier.
3. Have had any major bleeding episodes (variceal bleeds, hemorrhagic strokes, internal abdominal bleeds, etc.) within 6 months prior to starting study drug.
4. Known hypersensitivity to any study drug component (such as pegylated medications).
5. Extensive prior radiotherapy, more than 30% of bone marrow reserves, or prior bone marrow/stem cell transplantation.
6. Any concomitant condition that in the opinion of the investigator could compromise the objectives of this study and the patient's compliance.
7. Pregnant or lactating individuals.
8. Current malignancies of another type, with the exception of adequately treated in situ cervical cancer and basal cell skin cancer or other malignancies with no evidence of disease for 2 years or more.
9. Known history of HIV, HBV or HCV infection.
10. Documented or known bleeding disorder.
11. Requirement for anticoagulation treatment that increases INR or aPTT above the normal range (low dose DVT or line prophylaxis is allowed).
12. Clinically evident CNS metastases or leptomeningeal disease not controlled by prior surgery or radiotherapy; history of seizure disorder not controlled by anti-seizure medication at the time of enrollment. Patients with primary CNS malignancies are excluded.
13. Patients with a significant cardiovascular disease or condition, including:
1. Myocardial infarction within 6 months of study entry
2. NYHA Class III or IV heart failure
3. Uncontrolled dysrhythmias or poorly controlled angina.
4. History of serious ventricular arrhythmia (VT or VF, ≥ 3 beats in a row) and/or risk factors (e.g., heart failure, hypokalemia, family history of Long QT Syndrome)
5. Baseline prolongation of QT/QTc interval (repeated demonstration of QTc ≥ 450 msec for men and 470 msec for women). QTc values up to 500 msec will be acceptable where patient's medical history, e.g. bundle branch block, is known to cause mild QTc prolongation and the condition is well controlled
