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

Completed · Phase 1

Conditions studied: Urothelial Carcinoma

In brief

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 originally comprised 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 these patients. 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 urothelial carcinoma. 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 development. Part B of the study will no longer be conducted.

Key facts

Study ID: NCT03473756
Run by: Bayer
People needed: 37
Starts: 2018-05-15
Expected to finish: 2024-07-10
Last updated by the study team: 2025-04-09

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

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.

You may not qualify if…

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.

Where it is running

University of Arizona Cancer Center — Tucson, Arizona, United States
UChicago Medicine Comprehensive Cancer Center - Hyde Park — Chicago, Illinois, United States
Barbara Ann Karmanos Cancer Institute - Detroit Headquarters — Detroit, Michigan, United States
Memorial Sloan-Kettering Cancer Center — New York, New York, United States
Krankenhaus der Barmherzigen Brüder — Vienna, State of Vienna, Austria
Ordensklinikum Linz GmbH Elisabethinen — Linz, Upper Austria, Austria
Uniklinikum Salzburg - Landeskrankenhaus — Salzburg, Austria
Universitätsklinikum AKH Wien — Vienna, Austria
Institut Bergonie - Unicancer Nouvelle Aquitaine — Bordeaux, France
Centre Oscar Lambret - Lille — Lille, France
Institut de Cancérologie de l'Ouest - Saint Herblain — Saint-Herblain, France
Universitätsklinikum Köln — Cologne, North Rhine-Westphalia, Germany
Universitätsklinikum Essen — Essen, North Rhine-Westphalia, Germany
Universitätsmedizin der Johannes Gutenberg Universität Mainz — Mainz, Rhineland-Palatinate, Germany
Azienda Ospedaliero Universitaria di Modena — Modena, Emilia-Romagna, Italy
Fondazione IRCCS Istituto Nazionale dei Tumori — Milan, Lombardy, Italy
Istituto Europeo di Oncologia s.r.l - Sviluppo di nuovi farmaci per Terapie Innovative — Milan, Lombardy, Italy
Istituto Oncologico Veneto — Padova, Veneto, Italy
A.O.U.I. Verona — Verona, Veneto, Italy
National Cancer Center Hospital East — Kashiwa, Chiba, Japan
National Hospital Organization Shikoku Cancer Center — Matsuyama, Ehime, Japan
University of Tsukuba Hospital — Tsukuba, Ibaraki, Japan
The Cancer Institute Hospital of JFCR — Koto-ku, Tokyo, Japan
Severance Hospital, Yonsei University Health System — Seoul, Seoul Teugbyeolsi, South Korea
Asan Medical Center — Seoul, Seoul Teugbyeolsi, South Korea

Full record on ClinicalTrials.gov

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