Disitamab Vedotin With Pembrolizumab vs Chemotherapy in Previously Untreated Urothelial Cancer Expressing HER2

Inclusion Criteria: * Histopathological confirmation of locally advanced unresectable or metastatic urothelial carcinoma (LA/mUC), including UC originating from the renal pelvis, ureters, bladder, or urethra. * Measurable disease by investigator assessment per RECIST v1.1. * Participant must not have received prior systemic therapy for LA/mUC. Exception will be made for neoadjuvant or adjuvant therapy, if disease recurrence/progression occurred more than 12 months after the last dose of therapy. * Eligible to receive cisplatin- or carboplatin-containing chemotherapy. * Able to provide archived formalin-fixed paraffin-embedded tumor tissue blocks from a muscle-invasive or metastatic UC lesion or biopsy of metastatic UC prior to treatment initiation. If archival tissue is not available a newly obtained baseline biopsy of an accessible tumor lesion is required within 28 days of cycle 1 day 1. * HER2 expression of 1+ or greater on immunohistochemistry (IHC). * Eastern Cooperative Oncology Group (ECOG) performance score of 0, 1, or 2 within 7 days prior to randomization. Exclusion Criteria: * Known hypersensitivity to disitamab vedotin, cisplatin, carboplatin, gemcitabine, or pembrolizumab or any of their components. * History of severe/life threatening immune-related adverse event (irAE) with PD-(L)1 inhibitors are excluded. * Central nervous system (CNS) and/or leptomeningeal metastasis. Participants with treated CNS metastases are permitted if all of the following are met. …