A Study of Vepugratinib (LY3866288) in Participants With Cancer in the Urinary Tract

The purpose of this study is to test a new medicine, vepugratinib, in comparison with placebo, to see if it is safe and can help people with a bladder cancer that is advanced or has spread. Vepugratinib or placebo will be administered in combination with enfortumab vedotin and pembrolizumab. Study participation could last up to approximately 6 years.

Inclusion Criteria: * Have histologically confirmed, unresectable locally advanced or metastatic urothelial cancer (mUC). Individuals with mixed histology other than small cell or neuroendocrine carcinoma are eligible if a urothelial component is present. * Have a qualifying fibroblast growth factor receptor 3 (FGFR3) genetic alteration determined via molecular testing from a tumor or blood sample obtained at or any time after diagnosis of advanced or metastatic urothelial cancer. * Have measurable disease by investigator assessment defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 * Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2. * Have adequate laboratory parameters Exclusion Criteria: * Have received prior systemic therapy for locally advanced or metastatic urothelial cancer (mUC). * Have any unresolved toxicities greater than Grade 1 Common Terminology Criteria for Adverse Events (\[CTCAE\] version 5.0) from prior neoadjuvant or adjuvant systemic therapy. * Have ongoing sensory or motor neuropathy of Grade 2 or higher * Have untreated or uncontrolled central nervous system (CNS) involvement or any history of leptomeningeal disease. * Current evidence corneal keratopathy or retinal disorder confirmed by ocular examination at screening.