Urothelial CarcinomaPhase 1FORT-2NCT03473756
Phase 1b/2 Study of Rogaratinib (BAY1163877) in Combination With Atezolizumab in Urothelial Carcinoma
A Phase 1 study testing Rogaratinib (BAY1163877) and Atezolizumab in people with Urothelial Carcinoma, run by Bayer at 30 sites in 8 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Urothelial Carcinoma
- What is being tested?
- Rogaratinib (BAY1163877) and Atezolizumab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 37 participants
- Where
- 30 sitesin 8 countries
- Study dates
- 15 May 2018to 10 Jul 2024
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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
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- 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.
Trial locations and contacts
30 sites in 8 countries.
30 sites in 8 countries
Italy5 sites
Fondazione IRCCS Istituto Nazionale dei Tumori
Milan, Lombardy, 20133
Istituto Europeo di Oncologia s.r.l - Sviluppo di nuovi farmaci per Terapie Innovative
Milan, Lombardy, 20141
Azienda Ospedaliero Universitaria di Modena
Modena, Emilia-Romagna, 41100
Istituto Oncologico Veneto
Padova, Veneto, 35128
A.O.U.I. Verona
Verona, Veneto, 37134
United States4 sites
UChicago Medicine Comprehensive Cancer Center - Hyde Park
Chicago, Illinois, 60637
Barbara Ann Karmanos Cancer Institute - Detroit Headquarters
Detroit, Michigan, 48201
Memorial Sloan-Kettering Cancer Center
New York, New York, 10065
University of Arizona Cancer Center
Tucson, Arizona, 85724
Austria4 sites
Ordensklinikum Linz GmbH Elisabethinen
Linz, Upper Austria, 4020
Uniklinikum Salzburg - Landeskrankenhaus
Salzburg, 5020
Krankenhaus der Barmherzigen Brüder
Vienna, State of Vienna, 1020
Universitätsklinikum AKH Wien
Vienna, 1090
Japan4 sites
National Cancer Center Hospital East
Kashiwa, Chiba, 277-8577
The Cancer Institute Hospital of JFCR
Koto-ku, Tokyo, 135-8550
National Hospital Organization Shikoku Cancer Center
Matsuyama, Ehime, 791-0280
University of Tsukuba Hospital
Tsukuba, Ibaraki, 305-8576
Spain4 sites
Ciutat Sanitaria i Universitaria de la Vall d'Hebron
Barcelona, 08035
Hospital Clínic i Provincial de Barcelona
Barcelona, 8036
Hospital Ramón y Cajal | Oncología
Madrid, 28034
Hospital General Universitario de Valencia
Valencia, 46014
France3 sites
Institut Bergonie - Unicancer Nouvelle Aquitaine
Bordeaux, 33076
Centre Oscar Lambret - Lille
Lille, 59020
Institut de Cancérologie de l'Ouest - Saint Herblain
Saint-Herblain, 44800
Germany3 sites
Universitätsklinikum Köln
Cologne, North Rhine-Westphalia, 50937
Universitätsklinikum Essen
Essen, North Rhine-Westphalia, 45147
Universitätsmedizin der Johannes Gutenberg Universität Mainz
Mainz, Rhineland-Palatinate, 55101
South Korea3 sites
Severance Hospital, Yonsei University Health System
Seoul, Seoul Teugbyeolsi, 03722
Asan Medical Center
Seoul, Seoul Teugbyeolsi, 05505
Samsung Medical Center
Seoul, 06351
About this study
Official title: An International, Multicenter, Phase 1b/2 Study of Rogaratinib (BAY1163877) in Combination With Atezolizumab as First-line Treatment in Cisplatin-ineligible Patients With FGFR-positive Locally Advanced or Metastatic Urothelial Carcinoma
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.
Read more
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
- Being tested
- Rogaratinib (BAY1163877), Atezolizumab
- Keywords
- Locally advanced or metastatic urothelial carcinoma, Bladder cancer, Checkpoint inhibition, FGFR inhibition
- Medical subject headings
- Carcinoma, Transitional Cell, Urinary Bladder Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Rogaratinib (BAY1163877)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.
AtezolizumabDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Rogaratinib + Atezolizumab in Part A | Experimental | 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. Receives: Drug: Rogaratinib (BAY1163877); Drug: Atezolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Dose-limiting Toxicities(DLTs)
Measured: Up to 21 days
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Measured: up to 90 days after the last study medication intake, an average of 60 days
Number of Participants With Drug-related TEAEs
Measured: up to 90 days after the last study medication intake, an average of 60 days
Number of Participants With Treatment-emergent Serious Adverse Events(TESAEs)
Measured: up to 90 days after the last study medication intake, an average of 60 days
Secondary outcomes (3)
Objective Response Rate(ORR)
Objective response rate (ORR) was defined as the percentage of patients with complete response (CR) or partial response (PR). Patients for whom best overall tumor response was not CR or PR, as well as patients without any post-baseline tumor assessment were considered non-responders. For all patients, the best overall tumor response was determined locally by investigators using the RECIST (Response Evaluation Criteria In Solid Tumors) criteria. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Measured: Up to 5 months
Maximal Plasma Concentration (Cmax) of Rogaratinib
Measured: At cycle 1 Day 1
Area Under the Rogaratinib Concentration Versus Time Curve (AUC)
Measured: At cycle 1 Day 1, 0-t(last)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Mar 2018
- Study start15 May 2018
- Primary completion16 Jul 2021
- Study completion10 Jul 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Urothelial CarcinomaStudies of the same condition, open and under way.
- More trials run by BayerThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 37 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bayer
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03473756
- Sponsor's protocol ID
- 19131
- Other IDs
- 2017-001483-38, 2017
- Acronym
- FORT-2
- Status last verified
- Mar 2025
- First submitted
- 16 Mar 2018
- Last updated
- 9 Apr 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: Availability of this study's data will later be determined according to Bayer's commitment to the EFPIA/PhRMA "Principles for responsible clinical trial data sharing". This pertains to scope, timepoint and process of data access. As such, Bayer commits to sharing upon request from qualified researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the US and EU as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014. Interested researchers can use www.vivli.org to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the member section of the portal.
Publications
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.
PubMed 39298147Grunewald 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.
PubMed 30807645