A Study of Efficacy and Safety of Sacituzumab Tirumotecan (MK-2870) Plus Enfortumab Vedotin (EV) With and Without Pembrolizumab in Advanced Urothelial Carcinoma (MK-3475-04C/KEYMAKER-U04)

Inclusion Criteria:

The main inclusion criteria include but are not limited to the following:

• Must have histologically documented, locally advanced/metastatic urothelialcarcinoma (la/mUC).

• Must provide an archival tumor tissue sample or newly obtained core or excisionalbiopsy of a tumor lesion demonstrating UC, not previously irradiated, and adequatefor biomarker evaluation. A newly obtained biopsy is strongly preferred, but notrequired if archival tissue is evaluable.

• Any AEs due to previous anticancer therapies must have recovered to ≤Grade 1 orbaseline. Endocrine-related AEs adequately treated with hormone replacement areeligible.

• PART 1 ONLY: Participants must have received platinum-based chemotherapy fortreatment of la/mUC.

• PART 1 ONLY: Participants must not have received >2 lines of therapy for la/mUC.Platinum-based chemotherapy followed by avelumab maintenance is considered 2 linesof therapy.

• PART 2 ONLY: Participants must not have received prior systemic therapy for la/mUC.

Exclusion Criteria:

The main exclusion criteria include but are not limited to the following:

• Known additional malignancy that is progressing or has required active treatmentwithin the past 3 years.

• Known active central nervous system metastases and/or carcinomatous meningitis.

• Has Grade ≥2 peripheral neuropathy.

• Has history of documented severe dry eye syndrome, severe Meibomian gland diseaseand/or blepharitis, or severe corneal disease that prevents/delays corneal healing.

• Has active inflammatory bowel disease requiring immunosuppressive medication orprevious history of inflammatory bowel disease (eg, Crohn's disease, ulcerativecolitis, or chronic diarrhea).

• Has uncontrolled, significant cardiovascular disease or cerebrovascular diseaseand/or serious cardiovascular and cerebrovascular diseases within the 6 monthspreceding study intervention.

• Has active keratitis or corneal ulcerations. Superficial punctate keratitis isallowed if the disorder is being adequately treated in the opinion of theinvestigator.

• Has a history of uncontrolled diabetes.

• Has received an investigational agent or has used an investigational device within 4weeks prior to study intervention administration.

• Has received a live or live-attenuated vaccine within 30 days prior to the firstdose of study intervention.

• PART 2 ONLY: Has a diagnosis of immunodeficiency or is receiving chronic systemicsteroid therapy or any other form of immunosuppressive therapy within 7 days beforethe first dose of study intervention. Inhaled or topical steroids are permitted inthe absence of active autoimmune disease. Physiologic replacement doses ofcorticosteroids are permitted for participants with adrenal insufficiency.

• PART 2 ONLY: Has an active autoimmune disease that has required systemic treatmentin past 2 years except replacement therapy.

• Is human immunodeficiency virus (HIV)-infected and has a history of Kaposi's sarcomaand/or Multicentric Castleman's Disease.

• Has active Hepatitis B or Hepatitis C virus infection.

• Has a history of (noninfectious) pneumonitis/interstitial lung disease that requiredsteroids or has current pneumonitis/interstitial lung disease.

• Has an active infection requiring systemic therapy.

• PART 2 ONLY: History of allogeneic tissue/solid organ transplant.

• Has not adequately recovered from major surgery or has ongoing surgicalcomplications.