Neoadjuvant Sasanlimab With Radiation as an in Situ Vaccine for Cisplatin-ineligible Muscle Invasive Bladder Cancer

Inclusion Criteria: 1. Capable of giving signed informed consent 2. Age ≥ 18 years 3. ECOG Eastern Cooperative Oncology Group performance status 0-2 4. Predominant (\>50%) urothelial carcinoma histology 5. Muscle-invasive bladder cancer (cT2-4a, cN0, cM0) 6. Decline/refuse OR Ineligible to receive cisplatin-based Neoadjuvant Chemotherapy due to at least one of the following criteria: a. Creatinine clearance less than 60 mL/min b. Eastern Cooperative Oncology Group performance status of ≥ 2 c. Grade ≥ 2 hearing loss d. Grade ≥ 2 neuropathy 7. Adequate Bone Marrow Function (without hematopoietic growth factor support within 14 days prior to study screening), defined as: a. Absolute neutrophil count (ANC) ≥1,500/mm3 or ≥1.5 x 109/L b. Platelets ≥100,000/mm3 or 100 x 109/L c. Hemoglobin ≥9 g/dL (≥5.6 mmol/L) 8. Adequate renal function defined by an estimated creatinine clearance ≥30 mL/min according to the Cockcroft Gault formula or by 24-hour urine collection for creatinine clearance. 9. Adequate liver function, including: a. Aspartate and alanine aminotransferase (AST and ALT) ≤ 2.5 × the upper normal limit range (ULN) b. Total serum bilirubin ≤ 1.5 x ULN 10. Able to give informed consent and patient is willing and able to comply with scheduled study visits and treatment plan 11. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other procedures. 12. Meeting the following criteria for sex specific considerations: <!-- --> 1. Males - for the duration of study and for at least 6 months after the last dose of study drug (Sasanlimab): 1. Refrain from donating sperm and be abstinent from intercourse OR Agree to use male condom and also consider the benefit for a female partner to use a highly effective method of contraception as a condom may break or leak when having sexual intercourse with a woman of childbearing potential (WOCBP) who is not currently pregnant 2. Females: a) Eligible to participate if not pregnant or breast feeding AND Is not a woman of childbearing potential (WOCBP) OR Is a WOCBP and is using a contraceptive method that is highly effective (failure rate of \< 1% per year), with low user dependency during the during the study treatment and for at least 6 months after the last dose of study drug (Sasanlimab) b) A WOCBP must have a negative, highly sensitive (at least 25 IU/mL) pregnancy test by urine or serum testing within 24 hours before the first dose of study drug (Sasanlimab). In cases where the urine test cannot be confirmed to be negative, a serum pregnancy test will be used. Exclusion Criteria: 1. Lymphadenopathy (\>1cm short-axis measurement on CT/MRI Imaging or biopsy proven) 2. Metastatic disease 3. Prior systemic chemotherapy for bladder cancer (however, may have had intra-vesical chemotherapy such as gemcitabine, docetaxel or mitomycin-C) 4. Prior treatment with systemic anti-cancer investigational agent 5. Other malignancy within 2 years prior to study screening, or active malignancy except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the breast or of the cervix, or low-grade (Gleason 6 or below) prostate cancer on surveillance without any plans for treatment intervention (e.g., surgery, radiation, or castration) or other concurrent malignancy felt by the investigator has a very low likelihood to become metastatic 6. Previous radiation therapy to the bladder 7. Active or history of autoimmune disease which may deteriorate when receiving immune checkpoint blockade. 1. These autoimmune conditions include but are not limited to limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, or multiple sclerosis 2. Participants with diabetes type I, vitiligo, psoriasis, or hypo or hyperthyroid disease not requiring immunosuppressive treatment are eligible. 8. Severe active infections (e.g., pulmonary tuberculosis) requiring systemic therapeutic oral or IV antibiotics within 2 weeks prior to study entry. 9. Clinically significant, multiple or severe drug allergies, intolerance to topical corticosteroids 10. Current unstable liver or biliary disease, defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice, or cirrhosis. * NOTE: Stable chronic liver disease (including Gilbert's syndrome, asymptomatic gallstones, and chronic stable hepatitis B or C -e.g., presence of hepatitis B surface antigen \[HBsAg\] or positive hepatitis C antibody test result at screening) is acceptable. 11. Active, uncontrolled HIV/AIDS infection (well-controlled HIV patients may be allowed). 12. Prior immunotherapy with anti PD-1, anti PD-L1, anti PD-L2, or anti cytotoxic T- lymphocyte-associated antigen-4 (CTLA-4) antibody. Note: prior intra-vesical BCG therapy is acceptable. 13. Prior treatment with immune-stimulatory agents including interleukin (IL)-2, IL-15, interferon (INF)- γ. 14. Vaccination within 4 weeks from study screening and while on study treatment unless administration of inactivated vaccines. 15. Patients with a condition requiring systemic treatment with either corticosteroids (\>10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids, and adrenal replacement doses \>10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease. 16. Clinically significant (active) cardiovascular disease including the following: cerebral vascular accident/stroke \<6 months prior to screening; myocardial infarction \<6 months prior to screening; unstable angina; congestive heart failure (≥New York Heart Association Classification Class III); or serious cardiac arrhythmia (uncontrolled, clinically significant) requiring medication. 17. Q-T interval corrected for heart rate (QTc) \>450 msec for male participants or QTc \>470 msec for female participants or QTc \>480 msec in participants with right bundle branch block 18. Prior organ transplantation or allogenic stem cell transplantation. 19. Known history of: immune-mediated colitis, inflammatory bowel disease, pneumonitis, or pulmonary fibrosis. 20. Patients with intolerance to or who have had a severe (Grade ≥3) allergic or anaphylactic reaction to antibodies or infused therapeutic proteins 21. Pregnant female patients; breastfeeding female patients; male patients able to father children and female patients of childbearing potential who are unwilling or unable to use a highly effective method(s) of contraception as outlined in this protocol for at least 6 months after the last dose of Sasanlimab (PF-06801591)