A Phase I Study of Immune Checkpoint Inhibition (Anti-CTLA4 and/or Anti-PD-L1) in Combination With Radiation Therapy in Patients With Unresectable and Non-metastatic Pancreatic Cancer

Patients with unresectable, locally advanced adenocarcinoma of pancreas will receive Stereotactic Body Radiation Therapy (SBRT) at a dose of 6 Gy daily, for 5 days. In Cohort A, where MEDI4736 is given, subjects will receive 10 mg/kg of MEDI4736 every 2 weeks, on the same day as, but after the first dose of SBRT is delivered (within 4 hours). In Cohort B, where tremelimumab is given, subjects will receive 10 mg/kg of tremelimumab every 4 weeks, on the same day as, but after the first dose of SBRT is delivered (within 4 hours). In Cohort C, where MEDI4736 and tremelimumab are given in combination, subjects will receive 10 mg/kg of tremelimumab every 4 weeks, on the same day as, but after the first dose of SBRT is delivered (within 4 hours), followed by 10 mg/kg of MEDI4736 every 4 weeks.

Correlative Studies The investigators will evaluate immune changes in peripheral blood samples and in tumor biopsy fine needle aspirate (FNA) specimens pre- and post- treatment from the 3 cohorts that involve the combination of stereotactic body radiation therapy (SBRT) with either (A) MEDI4736 alone, (B) tremelimumab alone, or (C) the combination of MEDI4736 and tremelimumab. FNA biopsies will be done at baseline (within 30 days of treatment initiation) and Day 28 of cycle 2 (between days 22-28 of cycle 2).