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

- FGFR testing of patients will be performed at the investigators' discretion up to a
max. of 90 days prior to start of screening.

Investigators should ensure all patients will be eligible in terms of disease status and
lines of treatment within this timeframe.

- Documented urothelial carcinoma (transitional cell carcinoma) including urinary
bladder, renal pelvis, ureters, urethra meeting all of the following criteria

- Histologically or cytologically confirmed (patients with mixed histologies are
required to have a dominant transitional cell pattern.)

- Locally advanced (T4b, any N; or any T, N 2−3) or metastatic disease (any T, any
N and M1). Locally advanced bladder cancer must be unresectable i.e. invading the
pelvic 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 one
platinum-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 (Messenger ribonucleic acid) expression levels (RNAscope score of
3+ or 4+; measurement is part of this protocol) in archival or fresh Tumor biopsy
specimen

- 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 anti-cancer treatment within 4 weeks before randomization.

- More than two prior lines of systemic anti-cancer therapy for urothelial carcinoma

- Ongoing or previous treatment with anti-FGFR directed therapies (e.g. receptor
tyrosine kinase inhibitors including rogaratinib or FGFRspecific antibodies) or with
taxanes or vinflunine

- Unresolved toxicity higher than National Cancer Institute's Common Terminology
Criteria for Adverse Events, version 4.03 (CTCAE v.4.03) Grade 1 attributed to any
prior therapy/procedure excluding alopecia, anemia and/or hypothyroidism

- History or current condition of an uncontrolled cardiovascular disease including any
of 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 3
months before randomization)

- Myocardial infarction (MI) within past 6 months before randomization

- Unstable cardiac arrhythmias requiring anti-arrhythmic therapy. Patients with
arrhythmia under control with anti-arrhythmic therapy such as beta-blockers or
digoxin are eligible.

- Arterial or venous thrombotic events or embolic events such as cerebrovascular
accident (including transient ischemic attacks), deep vein thrombosis or pulmonary
embolism 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)

- Any hemorrhage / bleeding event ≥ CTCAE v.4.03 Grade 3 within 4 weeks before
randomization

- Current diagnosis of any retinal detachment, retinal pigment epithelial detachment
(RPED), serous retinopathy or retinal vein occlusion