A Study of Disitamab Vedotin Alone or With Pembrolizumab in Urothelial Cancer That Expresses HER2

Inclusion Criteria: Cohorts A and B * Histopathologically-confirmed, locally-advanced, unresectable or metastatic urothelial cancer (LA/mUC), including UC originating from the renal pelvis, ureters, bladder, or urethra * Participants must have received only 1 or 2 lines of prior systemic treatment for LA/mUC, including 1 line of platinum-containing chemotherapy * At least one measurable lesion by investigator assessment based on RECIST version 1.1. * HER2-expression status determined by the central laboratory to be IHC 1+, 2+ or 3+, in the provided tumor sample * Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1 Cohort C * Histopathologically-confirmed LA/mUC, including UC originating from the renal pelvis, ureters, bladder, or urethra * No prior systemic therapy for LA/mUC * Neoadjuvant or adjuvant therapy, including PD-(L)1 inhibitors, is acceptable, if disease recurrence/progression occurred more than 12 months after the last dose of systemic therapy * At least one measurable lesion by investigator assessment based on RECIST v1.1. * Participant is eligible to receive cisplatin- or carboplatin- containing chemotherapy per investigator evaluation * HER2-expression status determined by the central laboratory to be IHC 1+, 2+ or 3+, on the provided tumor tissue sample * ECOG performance status of 0, 1, or 2 Cohort D * Histopathologically-confirmed LA/mUC, including UC originating from the renal pelvis, ureters, bladder, or urethra * Based on a participant's eligibility to receive treatment with standard of care therapies in Japan, participants must have received all of the following lines of therapy for LA/mUC: * a. One prior line of platinum-containing chemotherapy. * b. Prior therapy with PD-(L)1 inhibitors as (neo)adjuvant therapy, first-line maintenance therapy or as second line treatment. * c. Prior enfortumab vedotin therapy. * At least one measurable lesion by investigator assessment based on RECIST v1.1. * ECOG performance status of 0 or 1 Cohort E * Histopathologically-confirmed LA/mUC, including UC originating from the renal pelvis, ureters, bladder, or urethra * No prior systemic therapy for LA/mUC * Neoadjuvant or adjuvant therapy, including PD-(L)1 inhibitors, is acceptable, if disease recurrence/progression occurred more than 12 months after the last dose of systemic therapy. * At least one measurable lesion by investigator assessment based on RECIST v1.1. * Participant is eligible to receive cisplatin- or carboplatin- containing chemotherapy per investigator evaluation * HER2-expression status determined by the central laboratory to be IHC 1+, 2+ or 3+, in the provided tumor sample * ECOG performance status of 0 or 1 Cohort G * Histopathologically-confirmed, locally-advanced, unresectable or metastatic urothelial cancer (LA/mUC), including UC originating from the renal pelvis, ureters, bladder, or urethra * Participants must have received only 1 or 2 lines of prior systemic treatment for LA/mUC, including 1 line of therapy containing enfortumab vedotin as monotherapy or in combination with pembrolizumab * The last administration of enfortumab vedotin must be 90 days from the start of study treatment. Intervening therapies are allowed between the final dose of enfortumab vedotin and the start of disitamab vedotin. * At least one measurable lesion by investigator assessment based on RECIST version 1.1. * HER2-expression status determined by the central laboratory to be IHC 1+, 2+ or 3+, in the provided tumor sample * Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1 Exclusion Criteria: Cohorts A and B * Known hypersensitivity to disitamab vedotin or any of their components * Prior antitumor treatment (including chemotherapy, radiotherapy, targeted therapy, immunotherapy etc.) within 2 weeks of start of study (defined as Cycle 1 Day 1 for Cohorts A and B) * Toxicity from a previous treatment has not returned to Grades 0 or 1 (except for Grade 2 alopecia) * Prior MMAE-based ADCs (eg, enfortumab vedotin) or HER2-directed therapy * Major surgery that has not fully recovered within 4 weeks prior to dose administration * Peripheral sensory or motor neuropathy ≥ Grade 2 at baseline Cohort C * Known hypersensitivity to disitamab vedotin, pembrolizumab, or any of their components * Prior antitumor treatment (including chemotherapy, radiotherapy, targeted therapy, immunotherapy etc.) within 2 weeks of start of study defined as Cycle 1 Day 1 for the single-arm part of Cohort C and as randomization date for the randomized part of Cohort C) * Toxicity from a previous treatment has not returned to Grades 0 or 1 (except for Grade 2 alopecia) * Prior MMAE-based ADCs (eg, enfortumab vedotin) or HER2-directed therapy * Major surgery that has not fully recovered within 4 weeks prior to dose administration * Peripheral sensory or motor neuropathy ≥ Grade 2 at baseline * Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study drug * Participants who have previously received any prior treatment with an agent directed to another stimulatory or co-inhibitory T cell receptor (including but not limited to CD137 agonists, CAR-T cell therapy, CTLA-4 inhibitors, or OX-40 agonists) are excluded. Cohort D * Known hypersensitivity to disitamab vedotin or any of their components * Prior antitumor treatment (including chemotherapy, radiotherapy, targeted therapy, immunotherapy etc.) within 2 weeks of start of study (defined as Cycle 1 Day 1 for Cohort D) * Toxicity from a previous treatment has not returned to Grades 0 or 1 (except for Grade 2 alopecia) * Prior HER2-directed therapy * Any prior history of ≥ Grade 3 non-hematological AEs related to prior therapy * Major surgery that has not fully recovered within 4 weeks prior to dose administration * Peripheral sensory or motor neuropathy ≥ Grade 1 at baseline Cohort E * Known hypersensitivity to disitamab vedotin, pembrolizumab, or any of their components * Prior antitumor treatment (including chemotherapy, radiotherapy, targeted therapy, immunotherapy etc.) within 2 weeks of start of study (defined as Cycle 1 Day 1 for Cohort E) * Toxicity from a previous treatment has not returned to Grades 0 or 1 (except for Grade 2 alopecia) * Any prior history of ≥ Grade 3 non-hematological AEs related to prior therapy * Prior MMAE-based ADCs (eg, enfortumab vedotin) or HER2-directed therapy * Major surgery that has not fully recovered within 4 weeks prior to dose administration * Peripheral sensory or motor neuropathy ≥ Grade 1 at baseline * Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study drug Cohort G * Known hypersensitivity to disitamab vedotin or any of their components * Prior antitumor treatment (including chemotherapy, radiotherapy, targeted therapy, immunotherapy etc.) within 2 weeks of start of study (defined as Cycle 1 Day 1 for Cohort G) * Toxicity from a previous treatment has not returned to Grades 0 or 1 (except for Grade 2 alopecia) * Prior HER2-directed therapy * Major surgery that has not fully recovered within 4 weeks prior to dose administration * Peripheral sensory or motor neuropathy ≥ Grade 2 at baseline There are additional inclusion and exclusion criteria. The study center will determine if criteria for participation are met.