Phase Ib Multicenter, Cohort Dose Escalation Trial to Determine the Safety, Tolerance and Preliminary Antineoplastic Activity of Gemcitabine Administered in Combination With Continuous Intravenous Doses of PRI-724, a CBP/ β- Catenin Inhibitor, to Patients With Advanced or Metastatic Pancreatic Adenocarcinoma Eligible for Second-Line Therapy After Failing First-Line Therapy With FOLFIRINOX (or FOLFOX)

Inclusion Criteria:

1. Male or female patients, > 18 years of age.

2. Patients with a documented (histologically- or cytologically-proven) epithelial
cell/adenocarcinoma of the pancreas that is relapsed, locally advanced, or
metastatic.

3. Patients with measurable or evaluable disease according to the response evaluation
criteria in solid tumors

4. Patients eligible for second-line therapy after failing first-line therapy with the
regimen FOLFIRINOX.

5. Patients with a malignancy that is currently not amenable to surgical intervention,
due to either medical contraindications or non-resectability of the tumor.

6. Patients with a Karnofsky Performance Status of 70% to 100% (or equivalent, Eastern
Cooperative Oncology Group [ECOG] performance status of 0 or 1); Performance Status
Evaluation), and an anticipated life expectancy of ≥ 3 months.

7. Patients, both male and female, who are either not of childbearing potential or who
agree to use a medically effective method of contraception during the study and for 3
months after the last dose of study drug.

8. Patients with the ability to understand and give written informed consent for
participation in this trial, including all evaluations and procedures as specified by
this protocol.

Exclusion Criteria:

1. Women who are pregnant or lactating. Women of child-bearing potential (WOCBP) and
fertile men with a WOCBP partner, not using adequate birth control.

2. Patients with islet cell tumors or other non-epithelial cell malignancies of the
pancreas.

3. Patients with known CNS (or leptomeningeal) metastases not controlled by prior
surgery or radiotherapy, or patients with symptoms suggesting CNS involvement for
which treatment is required.

4. Patients with an active second malignancy within the last 2 years with the exception
of:

- Treated, non-melanoma skin cancers

- Treated CIS of the breast or cervix

- Controlled, superficial bladder carcinoma

- T1a or b prostate carcinoma involving < 5% of resected tissue and PSA within
normal limits (WNL) since resection

5. Patients with any of the following hematologic abnormalities at baseline:

- Hemoglobin < 9.0 g/dL

- Absolute neutrophil count (ANC) < 1,500 per mm3

- Platelet count < 100,000 per mm3

6. Patients with any of the following serum chemistry abnormalities at baseline:

- Total bilirubin > 1.5× the ULN for the institution, unless considered due to
Gilbert's Syndrome

- AST or ALT > 3× the ULN for the institution (> 5× ULN if due to hepatic
involvement by tumor)

- Serum albumin < 2.5 g/dL

- Serum creatinine > 1.5× ULN (or a calculated creatinine clearance < 60
mL/min/1.73 m2)

7. Patients with a significant cardiovascular disease or condition, including:

- Congestive heart failure (CHF) currently requiring therapy

- Need for anti-arrhythmic therapy for a ventricular arrhythmias

- Severe conduction disturbances

- Angina pectoris requiring therapy

- Left ventricular ejection fraction (LVEF) < 50% by MUGA or echocardiogram

- QTcF interval > 450 msec (males) or > 470 msec (females)

- Uncontrolled hypertension (per Investigator's discretion)

- Class III or IV cardiovascular disease according to the New York Heart
Association's (NYHA) Functional Criteria.

- Myocardial infarction (MI) within 6 months prior to first study drug
administration

8. Patients with known osteopenia or osteoporosis.

9. Patients with a known or suspected hypersensitivity to either gemcitabine or any of
the components of PRI-724.

10. Patients with a history of human immunodeficiency virus (HIV) or active infection
with hepatitis B virus (HBV) or hepatitis C virus (HCV).

11. Patients with any other serious/active/uncontrolled infection, any infection
requiring parenteral antibiotics, or unexplained fever > 38ºC within 2 weeks prior to
first study drug administration.

12. Patients with inadequate recovery from acute toxicity associated with any prior
antineoplastic therapy

13. Patients with inadequate recovery from any prior surgical procedure, or patients
having undergone any major surgical procedure within 1 month prior to first study
drug administration.

14. Patients with any other life-threatening illness, significant organ system
dysfunction, or clinically significant laboratory abnormality, which, in the opinion
of the Investigator, would either compromise the patient's safety or interfere with
evaluation of the safety of the study drug

15. Patients with a psychiatric disorder or altered mental status that would preclude
understanding of the informed consent process and/or completion of the necessary
studies

16. Patients with the inability, in the opinion of the Investigator, to comply with the
protocol requirements