Durvalumab and "Booster" Radiation in Metastatic Adenocarcinoma of the Pancreas

Inclusion Criteria:

* Biopsy-proven metastatic pancreatic adenocarcinoma with progression through standard first-line chemotherapy. Chemotherapy given as part of prior chemoradiation does not count as a line of therapy. Chemotherapy given as part of prior chemoradiation in the setting of non-metastatic pancreatic cancer does not count as a line of therapy.
* At least 3 radiographically distinct pancreatic cancer lesions that are measurable by RECIST 1.1 criteria, including 2 that are eligible for RT.
* Lesions that will receive RT are separated by ≥3 cm and none \>7 cm in greatest dimension.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
* Life expectancy of ≥12 weeks.
* Adequate liver and kidney function.
* Adequate blood cell count.
* Female subjects must either be of non-reproductive potential or must have a negative serum pregnancy test upon study entry.
* Subject is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up

Exclusion Criteria:

* Involvement in the planning and/or conduct of the study
* Previous enrollment in the present study.
* Any previous treatment with a programmed cell death 1 or programmed cell death ligand 1 inhibitor including Durvalumab.
* Prior RT to any lesion that would receive RT on this protocol.
* Prior RT that could lead to an unacceptably high risk of clinically significant normal tissue injury due to high cumulative normal tissue dose as determined by the investigator.
* Subjects who have received more than 1 line of chemotherapy in the metastatic setting.
* History of another primary malignancy except for: 1) malignancy treated with curative intent and with no known active disease ≥3 years before the first dose of study drug and of low potential risk for recurrence; 2) adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease; 3) adequately treated carcinoma in situ without evidence of disease (e.g., cervical cancer in situ).
* Receipt of the last dose of anti-cancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies, other investigational agent) ≤14 days prior to the first dose of study drug.
* Mean QT interval corrected for heart rate (QTc) ≥470 ms calculated from 3 electrocardiograms (ECGs) using Fridericia's Correction.
* Current or prior use of immunosuppressive medication within 28 days before the first dose of Durvalumab, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid.
* Any unresolved toxicity (\> grade 2, Common Terminology Criteria for Adverse Events version 4.03) from previous anti-cancer therapy. Subjects with irreversible toxicity that is not reasonably expected to be exacerbated by the investigational product may be included (e.g., hearing loss, peripherally neuropathy).
* Any prior Grade ≥ 3 immune-related adverse event (irAE) while receiving any previous immunotherapy agent, or any unresolved immune-related adverse event (irAE) \>Grade 1.
* Active or prior documented autoimmune disease within the past 2 years NOTE: Subjects with vitiligo, Graves' disease, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded.
* Active or prior documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis)
* History of primary immunodeficiency.
* History of allogeneic organ transplant.
* History of liver cirrhosis and Child-Pugh class B or C.
* History of hypersensitivity to Durvalumab or any excipient.
* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active bleeding diatheses, any subject known to have evidence of acute or chronic hepatitis B, hepatitis C or human immunodeficiency virus (HIV), or psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the subject to give written informed consent.
* Known history of previous clinical diagnosis of tuberculosis
* History of leptomeningeal carcinomatosis
* Receipt of live attenuated vaccination within 30 days prior to study entry or within 30 days of receiving durvalumab
* Female subjects who are pregnant, breast-feeding or male or female patients of reproductive potential who are not employing an effective method of birth control
* Any condition that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results
* Symptomatic or uncontrolled brain metastases requiring concurrent treatment, inclusive of but not limited to surgery, radiation and/or corticosteroids.
* Subjects with uncontrolled seizures.
* Subjects with known radiation hypersensitivity syndromes such as Ataxia-Telangiectasia or Nijmegen Breakage Syndrome