- Existence of archival or fresh tumor biopsy specimen for FGFR1/3 mRNA expression
- 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
- 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
- Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0 or 1.
- 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
- Myocardial infarction (MI) within past 6 months before the first study drug
- 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,
- 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.