A Study of OT-101 With mFOLFIRINOX in Patients With Advanced and Unresectable or Metastatic Pancreatic Cancer

1. Diagnosis of pancreatic islet neoplasm, acinar cell carcinoma, non-adenocarcinoma (ie,lymphoma, sarcoma), adenocarcinoma originating from the biliary tree, or cystadenocarcinoma

2. Patient has experienced a decrease in ECOG PS between Screening visit and within 72 hours prior to Randomization

3. Patient on Coumadin and not willing to change to LMWH or oral Factor II or Xa inhibitor with t½ of less than 24 hours

4. History of prior malignancy, except for adequately treated in situ cancer, basal cell, squamous cell skin cancer, or other cancers (eg, breast and prostate) for which the patient has been disease-free for at least 3 years. Patients with prior cancer that is adequately controlled per the judgement of the Investigator will not be excluded from the study

5. Any serious medical condition, laboratory abnormality, psychiatric illness, or comorbidity that, in the judgment of the Investigator, would make the patient inappropriate for the study

6. Patients with abnormal electrocardiogram (ECG) at baseline (QT or QTc interval \>470 ms) will be excluded from this study. The eligibility of patients with ventricular pacemakers for whom the QT interval may not be accurately measurable will be determined on a case-by-case basis by the Sponsor's medical representative in consultation with the principal investigator.

7. Serious systemic fungal, bacterial, viral, or other infection that is not controlled or requires intravenous antibiotics

8. Known history of positivity (regardless of immune status) for human immunodeficiency virus(HIV)

9. Known history of chronic active or active viral hepatitis A, B, or C infection

10. Clinically significant bleeding within 2 weeks prior to Randomization (eg, gastrointestinal\[GI\] bleeding or intracranial hemorrhage)

11. Pregnant or lactating women

12. Myocardial infarction, coronary bypass surgery, or arterial thromboembolic events within the last 6 months prior to Randomization, symptomatic congestive heart failure (New York Heart Association Classification \>Class II, unstable angina, or unstable cardiac arrhythmia requiring medication

13. Clinically significant ascites defined as requiring ≥1 paracentesis every 2 weeks

14. Major surgery, defined as any surgical procedure that involves general anesthesia and a significant incision (ie, larger than what is required for placement of central venous access, percutaneous feeding tube, or biopsy) within 28 days prior to Randomization or anticipated surgery during the study period

15. Prior history of receiving immune checkpoint inhibitors (anti-CTLA4, anti-PD1, anti-PD-L1)

16. Peripheral neuropathy (\>Grade 1)

17. Known history of dihydropyrimidine dehydrogenase deficiency (DPD) - Dihydropyrimidine dehydrogenase (DPD) is the initial and rate-limiting enzyme in the catabolism of 5-fluorouracil (5-FU). Thus, patients with a DPD deficiency are at risk of developing severe 5-FU-associated toxicity

18. History or risk of autoimmune disease, including but not limited to systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegner´s granulomatosis, Sjogren´s syndrome, Bell´s palsy, Guillain-Barre syndrome, multiple sclerosis, vasculitis, or glomerulonephritis, except for psoriasis not requiring systemic therapy, vitiligo or alopecia areata, or hypothyroidism

1. Investigational agents other than the protocol drugs

2. Anti-coagulants (except for heparin to maintain the patency of central venous catheters)

3. Non-steroidal anti-inflammatory drugs

4. Clopidogrel (Plavix), dipyridamole (Persantine), or any other drug that inhibits platelet functions

20. History of allergic reactions or known hypersensitivity to compounds of similar chemical or biologic composition to OT-101 such as anti-sense oligonucleotides or siRNA

21. Patients who are unable to return for follow-up visits or obtain follow-up studies required to assess toxicity to therapy. Telemedicine visits are acceptable

22. Not willing and able to comply with study requirements including protocol mandated procedures and visits

23. Other contraindications as defined in the product label of the components of the mFOLFIRINOX treatment regimen

24. Participation in another investigational clinical trial within 30 days of receiving the last dose of investigational study drug

25. Clinically significant psychiatric disorders, legal incapacity or limited legal capacity

26. Patients with a primary immunodeficiency

27. Patients with active central nervous system (CNS) metastases. (Patients with adequately treated CNS metastases who are clinically stable for at least 6 weeks after discontinuation of corticosteroids may be eligible for enrollment with the approval of the Sponsor's medical representative and the principal investigator)

What this study is about