A Phase 2 Study of siG12D LODER in Combination With Chemotherapy in Patients With Locally Advanced Pancreatic Cancer

Inclusion Criteria: Age

1. Subject must be 18 years of age or older at the time of signing the informed consent. Type of Subject and Disease Characteristics
2. Histologically or cytologically confirmed adenocarcinoma of the pancreas.
3. Locally advanced pancreatic cancer stage III according to The American Joint Committeeon Cancer (AJCC) and defined as T4, N (any) and M0, according to the three factors, T (tumor), N (node involvement), and M (metastases), of the National ComprehensiveCancer Network TNM classification.
4. Allocated to receive one of the following chemotherapies: gemcitabine plusnab-paclitaxel, FOLFIRINOX or modified FOLFIRIONOX as first line treatment forpancreatic cancer.
5. Have a target tumor that is accessible for intratumoral administration by EUS asdetermined by the radiologist/gastroenterologist performing the EUS intratumoraladministration, according to The American Society for Gastrointestinal Endoscopy (ASGE) guidelines (https://www.asge.org/home/practice-support/guidelines).
6. Have measurable disease. Subject will have a histologically-confirmed disease and musthave clinically and/or radiographically documented measurable primary diseaseaccording to RECIST v1.1. At least one site of disease must be unidimensionallymeasurable. Diagnostic Assessments
7. Eastern Cooperative Oncology Group (ECOG) Performance Scale of ≤ 1.
8. Demonstrate adequate organ function as defined below:

• serum creatinine <1.6 mg/dL
• international normalized ratio (INR) < 1.5 U
• absolute neutrophil count (ANC) > 1.5 x 109/L
• platelets ≥ 100 x 109/L
• hemoglobin ≥ 9 mg/dL
• alanine transaminase (ALT) and aspartate aminotransferase (AST) ≤ 5 times upperlimit of normal (ULN)
• bilirubin ≤ 1.5 x ULN Sex

8. Male and/or female. Contraceptive use by men or women should be consistent with localregulations regarding the methods of contraception for those participating in clinicalstudies.
9. Women of childbearing potential (WOCBP): a negative serum or urine pregnancy testduring screening.
10. Subject of childbearing potential, if sexually active (both men and women) must agreeto use a barrier method of contraception, from the time of administration of the firsttreatment and for at least 8 weeks after EOT visit day. Informed Consent
11. Capable of giving signed informed consent which includes compliance with therequirements and restrictions listed in the informed consent form (ICF) and in thisprotocol.

Exclusion Criteria: Subjects are excluded from the study if any of the following criteria apply: Medical Conditions

1. Subjects with resectable pancreatic cancer.
2. Evidence of metastatic disease.
3. Other malignancy that would interfere with the current intervention.
4. Any evidence of ascites (beyond trace).
5. Bulky celiac adenopathy (≥2.5 cm) or non-adenocarcinoma histology.
6. Previously treated malignancies, except for adequately treated non-melanoma skincancer, in situ cancer, or other cancers from which the subject has been disease-freefor at least 2 years.
7. History of clinically significant coagulopathy.
8. Major surgery, other than diagnostic surgery, within 4 weeks prior to study entrywithout complete recovery.
9. New York Heart Association (NYHA) Class III or IV, cardiac disease, myocardialinfarction within 4 months prior to the first chemotherapy cycle Day 1, unstablearrhythmia or symptomatic peripheral arterial vascular disease.
10. Active, uncontrolled bacterial, viral, or fungal infections, requiring systemictherapy.
11. Known active infection with human immunodeficiency virus (HIV), hepatitis B virus, orhepatitis C virus.
12. Females who are pregnant or breast-feeding.
13. Concomitant disease or condition that could interfere with the conduct of the study,or that would, in the opinion of the Investigator, pose an unacceptable risk to thesubject in this study. Prior/Concomitant Therapy
14. Any prior therapy for the treatment of pancreatic malignancy (including chemotherapy,immunotherapy, vaccines, monoclonal antibodies, major surgery, or irradiation, whetherconventional or investigational).
15. Prior therapy with any hypoxic cytotoxic agent (hypoxia-targeting drugs).Prior/Concurrent Clinical Study Experience
16. Subjects who are participating or participated in an investigational drug or devicestudy (within 28 days prior to study entry from the last study dose date). Other Exclusions:
17. Unwillingness or inability to comply with the study protocol for any reason.
18. Known allergy to sesame oil.