Study of Rogaratinib (BAY1163877) vs Chemotherapy in Patients With FGFR (Fibroblast Growth Factor Receptor)-Positive Locally Advanced or Metastatic Urothelial Carcinoma

Inclusion Criteria:

• Existence of archival or fresh biopsy for FGFR testing. Mandatory FGFR testing ofpatients will be performed prior to start of screening. The timing of the FGFR test isat the discretion of the investigator. Investigators should ensure all patients willbe eligible in terms of disease status and lines of treatment.
• Documented urothelial carcinoma (transitional cell carcinoma) including urinarybladder, renal pelvis, ureters, urethra meeting all of the following criteria
• Histologically confirmed (Patients with mixed histologies are required to have adominant transitional cell pattern.)
• Locally advanced (T4, any N; or any T, N 2-3) or metastatic disease (any T, any Nand M1). Locally advanced bladder cancer must be unresectable i.e. invading thepelvic or abdominal wall (stage T4b) or presenting with bulky nodal disease (N2-3).
• ECOG (Eastern Cooperative Oncology Group) Performance Status of 0 or 1
• Disease progression during or following treatment with at least oneplatinum-containing regimen (patients should have been treated for at least 2 cycles).In patients who received prior adjuvant/ neoadjuvant platinum-containing chemotherapy,progression had to occur within 12 months of treatment.
• High FGFR1 or 3 mRNA expression levels in archival or fresh tumor biopsy specimenquantified as outlined in the lab manual
• At least 1 measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST v.1.1) in contrast enhanced (unless contraindicated) CT or MRI

Exclusion Criteria:

• Previous or concurrent cancer except
• cervical carcinoma in situ
• treated basal-cell or squamous cell skin carcinoma
• any cancer curatively treated > 3 years before randomization
• curatively treated incidental prostate cancer (T1/T2a)
• Ongoing or previous treatment with anti-FGFR directed therapies (e.g. receptortyrosine kinase inhibitors including rogaratinib or FGFR-specific antibodies) or withtaxanes or vinflunine
• More than two prior lines of systemic anti-cancer therapy for urothelial carcinomagiven for advanced unresectable/ metastatic disease
• Ongoing or previous anti-cancer treatment within 4 weeks before randomization.
• Unresolved toxicity higher than National Cancer Institute's Common TerminologyCriteria for Adverse Events, version 4.03 (CTCAE v.4.03) Grade 1 attributed to anyprior therapy/ procedure excluding alopecia, anemia and/ or hypothyroidism
• History or current condition of an uncontrolled cardiovascular disease including anyof the following conditions:
• Congestive heart failure (CHF) NYHA (New York Heart Association) > Class 2
• Unstable angina (symptoms of angina at rest) or new-onset angina (within last 3months before randomization)
• Myocardial infarction (MI) within past 6 months before randomization
• Unstable cardiac arrhythmias requiring anti-arrhythmic therapy. Patients witharrhythmia under control with anti-arrhythmic therapy such as beta-blockers ordigoxin are eligible.
• Arterial or venous thrombotic events or embolic events such as cerebrovascularaccident (including transient ischemic attacks), deep vein thrombosis or pulmonaryembolism within 3 months before randomization
• Current evidence of endocrine alteration of calcium phosphate homeostasis (e.g.parathyroid disorder, history of parathyroidectomy, tumor lysis, tumoral calcinosis,paraneoplastic hypercalcemia)
• Current diagnosis of any retinal detachment, retinal pigment epithelial detachment (RPED), serous retinopathy or retinal vein occlusion
• Any hemorrhage / bleeding event ≥ CTCAE v.4.03 Grade 3 within 4 weeks beforerandomization