FORT-2 is designed to evaluate safety, efficacy, RP2D and PK of rogaratinib in combination
with atezolizumab in patients with untreated FGFR-positive urothelial carcinoma. The study
comprises two separate parts: Phase 1b (Part A) and Phase 2 (Part B).The study parts differ
in design, objectives and treatment.
The primary objectives of this Phase 1b study (Part A) are to determine the safety,
tolerability,RP2D and pharmacokinetics of rogaratinib in combination with atezolizumab in
The primary objective of the Part B is to compare progression-free survival (PFS) according
to RECIST v1.1 of rogaratinib in combination with atezolizumab over placebo in combination
with atezolizumab in untreated patients with FGFR-positive locally advanced or metastatic
Of note, patients who participate in Part A are not allowed to participate in Part B.
Part B will be initiated once the data from Part A supports continuation of the study, even
if this occurs prior to primary completion of Part A. The sponsor may decide not to continue
the study as a whole after completion of Part A if the data do not support further
- 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.