Brief Title: Phase 1b/2 Study of Rogaratinib (BAY1163877) in Combination With Atezolizumab in Urothelial Carcinoma

PRIMARY OUTCOMES

Primary Outcome 1 - Measure: Number of Participants With Dose-limiting Toxicities(DLTs)

Primary Outcome 1 - Timeframe: Up to 21 days

Primary Outcome 2 - Measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs)

Primary Outcome 2 - Timeframe: up to 90 days after the last study medication intake

Primary Outcome 3 - Measure: Number of Participants With Drug-related TEAEs

Primary Outcome 3 - Timeframe: an average of 60 days

Primary Outcome 4 - Measure: Number of Participants With Treatment-emergent Serious Adverse Events(TESAEs)

Primary Outcome 4 - Timeframe: up to 90 days after the last study medication intake

CONDITION

• Urothelial Carcinoma

ELIGIBILITY

Inclusion criteria:
* Existence of archival or fresh tumor biopsy specimen for FGFR1/3 mRNA expression testing

- * High FGFR1 or 3 mRNA expression levels (RNAscope score of 3+ or 4+) in archival or fresh tumor biopsy specimen

- * Documented locally advanced (T4, any N; or any T, N2-3) or metastatic urothelial carcinoma (transitional cell carcinoma) including urinary bladder, renal pelvis, ureters, urethra, meeting all of the following criteria:

- * No prior systemic treatment for locally advanced or metastatic urothelial carcinoma. For patients who received prior adjuvant/neoadjuvant chemotherapy or chemo-radiation for urothelial carcinoma, a treatment-free interval > 12 months between the last treatment administration and the date of recurrence is required in order to be considered treatment-naïve in the metastatic setting. Prior local intra-vesical chemotherapy or prior local immunotherapy is allowed if completed at least 4 weeks before the first study drug administration. Regionally available standard of care options must be considered for all patients.

- * Ineligibility for cisplatin-based chemotherapy as defined by any one of the following criteria:
* Impaired renal function (GFR > 30 but < 60 mL/min/1.73 m2) according to the modification of diet in renal disease (MDRD) abbreviated formula - * A Hearing loss (measured by audiometry) of > 25 dB at two contiguous test frequencies in at least one ear.

- * Grade ≥ 2 peripheral neuropathy (i.e. sensory alteration or paresthesia including tingling)

- * Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0 or 1.
Exclusion criteria:
* Active symptomatic or untreated brain metastases as determined by CT or MRI evaluation during screening and prior radiographic assessment.

- * History of autoimmune disease, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with anti-phospholipid syndrome, granulomatosis with polyangiitis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis.

- * History or current condition of an uncontrolled cardiovascular disease including any of the following conditions:
* Congestive heart failure (CHF) NYHA Class 2 or greater, unstable angina (symptoms of angina at rest) or

- * New-onset angina (within last 3 months before the first study drug administration)

- * Myocardial infarction (MI) within past 6 months before the first study drug administration

- * Unstable cardiac arrhythmias requiring anti-arrhythmic therapy.

- * Patients with known coronary artery disease, congestive heart failure not meeting the above criteria, or known left ventricular ejection fraction < 50% must be on a stable medical regimen that is optimized in the opinion of the treating physician, in consultation with a cardiologist if appropriate. - * Current diagnosis of any retinal disorders including retinal detachment, retinal pigment epithelial detachment (RPED), serous retinopathy or retinal vein occlusion. - * Current evidence of endocrine alteration of calcium phosphate homeostasis (e.g. parathyroid disorder, history of parathyroidectomy, tumor lysis, tumoral calcinosis, paraneoplastic hypercalcemia). - * Concomitant therapies that are known to increase serum calcium or phosphate levels (i.e. antacids, phosphate-containing laxatives oral/rectal, potassium phosphate) and that cannot be discontinued or switched to a different medication before the first study drug administration - * Treatment with systemic corticosteroids or other systemic immunosuppressant medications within 2 weeks before the first study drug administration, or anticipated requirement for systemic immunosuppressive medications during the trial.

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

OFFICIAL INFORMATION

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LOCATION