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

This is a single-institution phase II trial of durvalumab combined with Radiation Therapy
(RT) for metastatic pancreatic cancer patients who have progressed through first-line
chemotherapy. Pancreatic cancer patients who have received second-line or greater
chemotherapy in the metastatic setting are not eligible. Target accrual is 39 patients.
Durvalumab 1500 mg (or 20 mg/m2 if <30 kg) IV Q4W will be started and continued during RT and
afterwards until the patient experiences either unacceptable toxicity or disease progression,
whichever comes first. Patients must have at least three radiographically measurable
pancreatic cancer lesions in different organs that have not previously received RT, two of
which will receive RT. Eligible lesions include either the primary pancreatic tumor in
unresected patients or distant metastatic lesions. Three fractions of 8 Gy each will be
prescribed to one lesion during Week 3. Three fractions of 8 Gy each will be prescribed to
the second lesion during Week 5.

This is a single-arm trial with continuous monitoring of acute non-hematologic toxicity with
the primary endpoint of progression free survival. Efficacy will be evaluated by time to
progression or death, whichever comes first, and compared to historical control of
chemotherapy alone as reported in the literature.

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.

- 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.

Exclusion Criteria:

- Previous enrollment in the present study.

- Any previous treatment with a PD-1 or PD-L1 inhibitor including durvalumab.

- Prior RT to any lesion that would receive RT on this protocol.

- 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).

- 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 prior Grade ≥3 immune-related adverse event (irAE) while receiving any previous
immunotherapy agent, or any unresolved irAE >Grade 1.