A Clinical Trial of Sacituzumab Tirumotecan (Sac-TMT, MK-2870) and Pembrolizumab (MK-3475A) in Participants With Bladder Cancer (MK-2870-055)

Researchers are looking for new ways to treat muscle-invasive bladder cancer (MIBC). MIBC is a type of bladder cancer that has spread into the muscle layer of the bladder but has not spread to other distant parts of the body. The usual treatment for MIBC is surgery to remove the bladder but some people choose to have other treatments, such as chemoradiotherapy (CRT), instead of surgery so they can keep their bladder. Researchers want to know if giving 2 trial treatments with CRT can treat MIBC. One trial treatment is called sacituzumab tirumotecan (sac-TMT) and the other trial treatment is called subcutaneous (SC) pembrolizumab (or pembrolizumab and berahyaluronidase alfa). The main goal of this trial is to learn if participants who receive sac-TMT, SC pembrolizumab, and CRT live longer without their cancer growing, spreading, or coming back compared to those who receive CRT alone.

Inclusion Criteria: The main inclusion criteria include but are not limited to the following: * Has a diagnosis of muscle-invasive bladder cancer (MIBC) (cT2-T4aN0-N1) * Has clinically nonmetastatic bladder cancer (N0-N1M0) * Is either ineligible for radical cystectomy or has opted for bladder preservation and is planned to receive chemoradiotherapy (CRT) * Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 Exclusion Criteria: The main exclusion criteria include but are not limited to the following: * Has known presence of diffuse carcinoma in situ (CIS) throughout the bladder * Has history of documented severe dry eye syndrome, severe Meibomian gland disease and/or blepharitis, or severe corneal disease that prevents/delays corneal healing * Has active inflammatory bowel disease requiring immunosuppressive medication or previous history of inflammatory bowel disease * Has uncontrolled, significant cardiovascular disease or cerebrovascular disease * Has received prior pelvic/local radiation therapy for any reason or any systemic antineoplastic treatment for MIBC * Has not recovered to Grade ≤1 or baseline from AE associated with anticancer therapy before randomization * Has a known additional malignancy that is progressing or has required active treatment within the past 2 years * Has a history of (noninfectious) pneumonitis/interstitial lung disease (ILD) that required steroids, has current pneumonitis/interstitial lung disease, or has suspected ILD or pneumonitis that cannot be ruled out by standard diagnostic assessments