The purpose of this study is to assess the safety, tolerability and efficacy of XER-001 and identify a best dose for future studies.

The primary objective of the phase 1 component of the study is to evaluate the safety, tolerability, and PK of nasoduodenal administration of XER-001 in conjunction with stereotactic body radiotherapy (SBRT) in patients with LAPC. The primary objective of the phase 2a component of the study is to evaluate safety and efficacy of combination SBRT and XER-001 with increasingly-liberalized duodenal radiation dose constraints.

Inclusion Criteria:

1. Cytologic or biopsy confirmed adenocarcinoma of the pancreas

2. Disease deemed amenable to definitive treatment with SBRT by being:

   1. Locally-advanced and/or technically unresectable, as determined by a specialist pancreaticobiliary surgeon and as part of a multidisciplinary team review including of multiphase cross-sectional imaging, demonstrating: i. Greater than 180-degree tumor involvement of the superior mesenteric artery (SMA) ii. Greater than 180-degree tumor involvement of the celiac axis including major branches of the celiac axis that would render the tumor unresectable (e.g. common hepatic artery) iii. Tumor involvement of the first branch of the SMA that is not surgically reconstructible iv. Long segment involvement of the superior mesenteric vein/portal vein/hepatic artery that is not amenable to surgical reconstructible.

   2. Potentially resectable anatomically but deemed not a surgical candidate after multidisciplinary review (such as unresectable due to comorbid conditions that render.

      the risks of surgery prohibitive)

   3. Potentially resectable but the patient elects to refuse surgery and prefers to pursue SBRT, and disease is deemed eligible for SBRT

3. Primary tumor involvement abutment of the bowel is allowed, however bowel infiltration or invasion (identified endoscopically or by contrast enhanced imaging) is not allowed.

4. No distant metastatic disease either prior to or following induction systemic therapy

5. Completion of medically indicated first line systemic therapy, which may include but is not limited to regimens such as FOLFIRNOX, gemcitabine/abraxane, and similar regimens

6. Patients must be able to understand and comply with any treatment related procedures for SBRT. including breath-hold techniques or tolerance of compression belt, or other motion management strategies for SBRT delivery.

7. Age 18 years or older

8. Eastern Cooperative Group (ECOG) performance status 0, 1, or 2

9. Adequate hematologic function as indicated by:

   1. Absolute neutrophil counts >/= 1500/mm3
   2. Hemaglobin >/= 8.0 g/dL
   3. Plor current use of hepato atelet count >/= 75,000/mm3

10. No known liver disease or hepatic impairment, as well as no recent or current use of hepatotoxic drugs or substances that could compromise liver function unless a washout period has been completed. Adequate liver function as indicated by:

    1. Total bilirubin </= 1.5x upper limits of normal (per institutional laboratory reference standard)
    2. Aspartate aminotransferase (AST) and alanine aminotranferase (ALT) </= 2.5 upper limits of normal (per institutional reference standard)

11. Baseline serum calcium level >/= 8.4 mg/dL

12. No clinically significant history or presence of safety 12-lead ECG findings as judged by the investigator at screening and check-in(s), including each criterion as listed below:

    1. Normal sinus rhythm (heart rate between 40 and 100 bpm)
    2. QTcF interval \