N-803 Alone or in Combination With BN-Brachyury Vaccine or Bintrafusp Alfa (M7824) for Participants With Castration Resistant Prostate Cancer

Background: Prostate cancer does not trigger a strong immune response in the body. Hormone therapy, to reduce levels of testosterone in the body, can be helpful to treat some prostate cancers. However, castration-resistant prostate cancer (CRPC) keeps growing even when the testosterone is reduced to a very low level. Men with metastatic CRPC survive an average of only 3 years. More effective treatments are needed. Objective: To test whether an immunotherapy drug (N-803), alone or in combination with other drugs, can help treat CRPC. Eligibility: Males aged 18 or older with CRPC. Prior treatment with testosterone-lowering therapy is required. Design: Participants will be screened. They will have blood and urine tests. They will have a CT scan of the chest, abdomen, and pelvis. They will continue to receive hormone therapy for prostate cancer. Participants will come to the NIH clinic once a week for the first 4 weeks. Then they will come once every 2 weeks. Visits will last up to 8 hours. The study will continue up to 3 years. All participants will receive N-803 once every 2 weeks. The drug is injected just under the skin with a small needle. Some participants will receive N-803 plus another drug (brachyury vaccine). This drug is also injected under the skin with a small needle. Some participants will receive N-803 plus a different drug (bintrafusp alfa) once every 2 weeks. This drug is given through a tube attached to a needle placed in a vein in the arm. Some participants may receive all 3 drugs. Participants will have imaging scans every 12 weeks.