Inclusion Criteria:  Expected survival ≥12 weeks Histologically confirmed locally advanced unresectable or metastatic urothelial cancer (UC), including UC originating from the renal pelvis, ureters, bladder, or urethra  Participant has received 1 or 2 lines of prior treatment for advanced UC, including 1 line of platinum-containing chemotherapy  Neoadjuvant or adjuvant therapy, with progression within 12 months of completing therapy, is considered a line of prior therapy. Maintenance avelumab therapy delivered following first-line platinum therapy is not considered a separate line of therapy. Prior therapy with PD-(L)1 inhibitors as (neo)adjuvant therapy, first line maintenance therapy or as second line treatment are allowed Radiographically documented disease progression during or after the most recent line of therapy for advanced disease At least one measurable lesion based on RECIST version 1.1. HER2-expressing status determined by the central laboratory to be IHC 1+, 2+ or 3+, in the most recent archival or fresh tumor sample Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1  Exclusion Criteria:  Known hypersensitivity to disitamab vedotin or any of its components Prior anti-tumor treatment (including chemotherapy, radiotherapy, targeted therapy, immunotherapy etc.) within 3 weeks of start of study Toxicity from a previous treatment has not returned to Grade 0-1 (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  Other malignant tumors within 5 years of study treatment, except for:  Prostate cancer treated with definitive intent (surgically or with radiation therapy) at ≥ 1 year prior to treatment initiation is acceptable Malignancies that can be cured after treatment  There are additional inclusion and exclusion criteria. The study center will determine if criteria for participation are met.