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

NCT ID: NCT03473756

Last Updated: 2025-04-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 37 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-05-15
• Study Completion Date: 2024-07-10

Brief Summary

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.

Conditions

Urothelial Carcinoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Rogaratinib + Atezolizumab in Part A

Part A: Part A is conducted in patients who are cisplatin-ineligible and have had no prior systemic treatment for locally advanced or metastatic disease.

Patients will receive rogaratinib plus atezolizumab combination treatment.

Group Type: EXPERIMENTAL

Rogaratinib (BAY1163877)

Intervention Type: DRUG

Part A:Rogaratinib will be administered orally until disease progression, unacceptable toxicity or consent withdrawal. The starting dose of 800 mg b.i.d. will be confirmed using a dose selection design.

Atezolizumab

Intervention Type: DRUG

Part A: A fixed dose of 1200 mg atezolizumab will be administered through intravenous (i.v.) infusion on Day 1 of each 21-day cycle until disease progression, unacceptable toxicity or consent withdrawal.

Interventions

Rogaratinib (BAY1163877)

Part A:Rogaratinib will be administered orally until disease progression, unacceptable toxicity or consent withdrawal. The starting dose of 800 mg b.i.d. will be confirmed using a dose selection design.

Intervention Type: DRUG

Atezolizumab

Part A: A fixed dose of 1200 mg atezolizumab will be administered through intravenous (i.v.) infusion on Day 1 of each 21-day cycle until disease progression, unacceptable toxicity or consent withdrawal.

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bayer

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

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

Ordensklinikum Linz GmbH Elisabethinen

Linz, Upper Austria, Austria

Krankenhaus der Barmherzigen Brüder

Vienna, Vienna, 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

Padua, 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

Samsung Medical Center

Seoul, , South Korea

Ciutat Sanitaria i Universitaria de la Vall d'Hebron

Barcelona, , Spain

Hospital Clínic i Provincial de Barcelona

Barcelona, , Spain

Hospital Ramón y Cajal | Oncología

Madrid, , Spain

Hospital General Universitario de Valencia

Valencia, , Spain

Countries

United States; Austria; France; Germany; Italy; Japan; South Korea; Spain

References

Sweis RF, Gajate P, Morales-Barrera R, Lee JL, Necchi A, de Braud F, Penel N, Grunwald V, Maruzzo M, Meran J, Ishida TC, Bao W, Zhou Y, Ellinghaus P, Rosenberg JE. Rogaratinib Plus Atezolizumab in Cisplatin-Ineligible Patients With FGFR RNA-Overexpressing Urothelial Cancer: The FORT-2 Phase 1b Nonrandomized Clinical Trial. JAMA Oncol. 2024 Nov;10(11):1565-1570. doi: 10.1001/jamaoncol.2024.3900. Epub 2024 Sep 19.

Reference Type: DERIVED

PMID: 39298147 (View on PubMed)

Grunewald S, Politz O, Bender S, Heroult M, Lustig K, Thuss U, Kneip C, Kopitz C, Zopf D, Collin MP, Boemer U, Ince S, Ellinghaus P, Mumberg D, Hess-Stumpp H, Ziegelbauer K. Rogaratinib: A potent and selective pan-FGFR inhibitor with broad antitumor activity in FGFR-overexpressing preclinical cancer models. Int J Cancer. 2019 Sep 1;145(5):1346-1357. doi: 10.1002/ijc.32224. Epub 2019 Mar 13.

Reference Type: DERIVED

PMID: 30807645 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2017-001483-38

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

19131

Identifier Type: -

Identifier Source: org_study_id