Immune Checkpoint Inhibitor M7824 and the Immunocytokine M9241 in Combination With Stereotactic Body Radiation Therapy (SBRT) in Adults With Advanced Pancreas Cancer

Background: Fewer than 10 percent of people with pancreas cancer can have surgery. Surgery gives the best outcome. Radiation therapy is usually used to make surgery possible. But it does not work for most people. Adding immunotherapy might help. Objective: To find a safe combined dose of Bintrafusp Alfa (M7824), NHS-IL12 (M9241, and radiation and to see if it causes pancreas cancer tumors to shrink. Eligibility: People ages 18 and older who have pancreas cancer and cannot have curative surgery Design: Participants will be screened under protocol 01-C-0129 with: Medical history Physical exam Heart, urine, and blood tests Scans. For this, participants will lie in a machine that takes pictures of the body. They may receive a contrast agent by vein. Possible tumor biopsy Participants will take the study drugs either alone or with radiation. They will get M7824 by vein every 2 weeks. They will get M9241 injected under the skin every 4 weeks. Participants who get radiation will get it 5 days in a row the first month. Participants will have visits every 2 weeks. They will repeat screening tests. If participants tumors shrink, they will have surgery. If their whole tumor is removed, they will stop treatment. They will otherwise continue treatment as long as they can tolerate it and it is helping them. Participants will have visits 1 week and 1 month after they stop treatment. Then they will be contacted by phone or email for life. If they stop treatment for a reason other than their disease getting worse, they will have scans every 12 weeks.