• Participants are eligible to be included in the study only if all of the following criteria apply:

‣ Male/female participants who are at least 18 years of age on the day of signing informed consent and who have a first confirmed diagnosis of MIBC with predominant urothelial histology obtained via a diagnostic or maximal TURBT within 90 days prior to enrollment.

‣ Note: Participants with mixed histology are eligible provided the urothelial component is ≥50%.

⁃ Has clinically non-metastatic bladder cancer (N0M0) determined by imaging (CT of the chest and CTU/MRU of abdomen and pelvis), assessed by the site.

⁃ Male participants:

‣ A male participant must agree to use a contraception and not to donate sperm during the administration of MK-3475 and ASG-22CE and for at least 90 days after the last dose of MK-3475 and for 6 months after ASG-22CE.

⁃ Female participants:

‣ A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:

∙ Not a woman of childbearing potential (WOCBP) OR

∙ A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 120 days after the last dose of MK3475 and for 6 months after ASG-22CE and RT.

⁃ The participant provides written informed consent for the trial.

⁃ Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Evaluation of ECOG is to be performed within 7 days prior to the first dose of study intervention.

⁃ Demonstrates adequate organ function. All screening laboratory tests should be performed within 10 days prior to the first dose of study intervention.