A Study of Erdafitinib in Participants With Metastatic or Locally Advanced Urothelial Cancer

A Phase 1b-2 Study to Evaluate Safety, Efficacy, Pharmacokinetics, and Pharmacodynamics of Various Regimens of Erdafitinib in Subjects With Metastatic or Locally Advanced Urothelial Cancer

The purpose of this study is to: (a) characterize the safety and tolerability of and to identify the recommended Phase 2 dose (RP2D) and schedule for erdafitinib in combination with cetrelimab, and for erdafitinib in combination with cetrelimab and platinum (cisplatin and carboplatin) chemotherapy and; (b) to evaluate the safety and clinical activity of erdafitinib alone and in combination with cetrelimab in cisplatin-ineligible participants with metastatic or locally advanced urothelial cancer (UC) with select fibroblast growth factor receptor (FGFR) gene alterations and no prior systemic therapy for metastatic disease.

Study Overview

• Status: Active, not recruiting
• Conditions: Urothelial Carcinoma
• Intervention / Treatment: Drug: Erdafitinib; Drug: Cetrelimab; Drug: Cisplatin; Drug: Carboplatin

Detailed Description

This open-label (all people know identity of intervention) and multicenter (when more than one hospital or medical school team work on a medical research study) study to establish the recommended phase 2 dose (RP2D) for erdafitinib and cetrelimab and/or platinum (cisplatin or carboplatin) chemotherapy, and to evaluate the safety of erdafitinib in combination with cetrelimab and platinum chemotherapy in Phase 1b and to evaluate the safety and efficacy of the RP2D of erdafitinib plus cetrelimab versus erdafitinib in Phase 2 in participants with advanced urothelial cancer with select fibroblast growth factor receptor (FGFR) gene alterations. Participants enrolled in Phase 1b erdafitinib + cetrelimab cohort may have received any number of lines of prior therapy, and participants enrolled in Phase 1b erdafitinib + cetrelimab + platinum chemotherapy cohort will have had no prior systemic therapy for metastatic disease and participants enrolled in Phase 2 will have had no prior systemic therapy for metastatic disease and will be cis-ineligible. Part 1 (Phase 1b: Dose Escalation) will identify safety and RP2Ds of erdafitinib + cetrelimab and erdafitinib + cetrelimab + platinum (cisplatin or carboplatin) chemotherapy, and Part 2 (Phase 2: Dose Expansion) will evaluate erdafitinib monotherapy and the RP2D regimen of the erdafitinib + cetrelimab combination to further characterize safety and clinical activity. The study will be conducted in 3 phases: screening phase, treatment phase, and follow-up phase. Study evaluations include efficacy, pharmacokinetics, pharmacodynamics, immunogenicity, biomarkers, and safety.

• Study Type: Interventional
• Enrollment (Actual): 125
• Phase: Phase 2; Phase 1

Expanded Access

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Contacts and Locations

Study Locations

• Belarus
  • Brest, Belarus, 224027
    • Brest Regional Oncology Dispensary
  • Grodno, Belarus, 230017
    • Grodno University Hospital
  • Homyel, Belarus, 246012
    • Gomel Regional Clinical Oncology Dispensary
  • Lesnoy, Belarus, 223040
    • State Institution N.N. Alexandrov Republican Scientific and
  • Minsk, Belarus, 220013
    • Minsk city Clinical Oncological Dispensary
  • Mogilev, Belarus, 212018
    • Mogilev Regional Hospital
  • Vitebsk, Belarus, 210603
    • Vitebsk Regional Clinical Hospital
• Belgium
  • Brussels, Belgium, 1200
    • Cliniques Universitaires Saint Luc
  • Brussels, Belgium, 1070
    • ULB Hôpital Erasme
  • Haine-Saint-Paul, Belgium, 7100
    • Jolimont
  • Kortrijk, Belgium, 8500
    • Az Groeninge
  • Liège, Belgium, 4000
    • CHU de Liège - Domaine Universitaire du Sart Tilman
  • Sint-Niklaas, Belgium, 9100
    • AZ Nikolaas - Campus Sint-Niklaas Moerland
  • Wilrijk, Belgium, 2610
    • GZA Ziekenhuizen- Campus St Augustinus
• Brazil
  • Barretos, Brazil, 14784-400
    • Fundacao Pio XII
  • Belo Horizonte, Brazil, 30150-221
    • Santa Casa de Misericordia de Belo Horizonte
  • Curitiba, Brazil, 81520 060
    • Liga Paranaense de Combate ao Cancer
  • Fortaleza, Brazil, 60170-170
    • Oncocentro Servicos Medicos e Hospitalares Ltda - Oncocentro
  • Rio de Janeiro, Brazil, 22250 905
    • Oncoclinicas Rio de Janeiro S A
  • Rio de Janeiro, Brazil, 22775 001
    • Instituto de Educacao, Pesquisa e Gestao em Saude Instituto Americas (COI)
  • Santo André, Brazil, 09060-650
    • CEPHO Centro de Estudos e Pesquisa de Hematologia e Oncologia
• France
  • Angers, France, 49055
    • Institut de Cancerologie de Ouest (ICO) Site Paul Papin
  • Bordeaux, France, 33075
    • Hopital Saint André
  • Caen, France, 14000
    • Centre Francois Baclesse
  • La Rochelle, France, 17019
    • Centre Hospitalier Saint Louis
  • Lyon, France, 69008
    • Centre Léon Bérard
  • Marseille, France, 13005
    • APHM Hopital Timone
  • Paris, France, 75015
    • Hôpital Européen Georges Pompidou
  • Strasbourg, France, 67000
    • Clinique Sainte Anne
  • Tours, France, 37044
    • CHRU de Tours
  • Vandœuvre-lès-Nancy, France, 54519
    • Institut de Cancerologie de Lorraine
  • Villejuif, France, 94800
    • Institut Gustave Roussy
• Italy
  • Bergamo, Italy, 24125
    • Cliniche Humanitas Gavazzeni
  • Candiolo, Italy, 10060
    • Istituto di Candiolo, IRCCS
  • Carpi, Italy, 41012
    • Ospedale Di Zona B Ramazzini
  • Catania, Italy, 95126
    • UOS Oncologia Medica, A.O. Cannizzaro
  • Ferrara, Italy, 44124
    • Arcispedale S. Anna Ferrara
  • Lecco, Italy, 23900
    • PO A.Manzoni di Lecco, ASST Lecco - Oncologia Medica - Lecco
  • Livorno, Italy, 57122
    • Ospedale Civile di Livorno
  • Milan, Italy, 20132
    • Irccs Ospedale San Raffaele
  • Milan, Italy, 20162
    • ASST Grande Ospedale Metropolitano Niguarda
  • Perugia, Italy, 06132
    • Ospedale S. Maria Della Misericordia Centro Operativo Studi Clinici SC Oncologia Medica
  • Piacenza, Italy, 29121
    • AUSL DI PIACENZA - Ospedale Guglielmo da Saliceto
  • Roma, Italy, 00128
    • Campus Bio Medico di Roma
  • Sondrio, Italy, 23100
    • Azienda Socio Sanitaria Territoriale (ASST) della Valtellin
  • Terni, Italy, 05100
    • Azienda Ospedaliera S. Maria Terni
  • Udine, Italy, 33100
    • Azienda Ospedaliero Universitaria S.Maria Della Misericordia
• Poland
  • Konin, Poland, 62-500
    • Przychodnia Lekarska KOMED Roman Karaszewski
  • Lodz, Poland, 93 513
    • Wojewodzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im M Kopernika w Lodzi
  • Warsaw, Poland, 02-507
    • Centralny Szpital Kliniczny MSWiA w Warszawie
  • Warsaw, Poland, 01-748
    • LUX MED Onkologia Sp. z o.o.
• Russia
  • Barnaul, Russia, 656049
    • Altai Regional Oncology Dispensary
  • Ivanovo, Russia, 153040
    • Ivanovo Regional Oncology Dispensary
  • Kislino Village, Russia, 305524
    • GUZ Kursk Regional Oncology Dispensary
  • Kuzmolovsky, Russia, 188663
    • Leningrad Regional Oncology Dispensary
  • Moscow, Russia, 105077
    • City Clinical Hospital n.a. D.D.Pletnev
  • Moscow, Russia, 117997
    • Russian Scientific Center of Roentgenoradiology
  • Moscow, Russia, 125130
    • Moscow City Clinical Hospital # 62
  • Nizhny Novgorod, Russia, 603000
    • Clinical Diagnostic Centre of Nizhny Novgorod Region
  • Nizhny Novgorod, Russia, 603074
    • Privolzhsky District Medical Centre
  • Omsk, Russia, 644013
    • Clinical Oncology Dispensary
  • Pyatigorsk, Russia, 357500
    • LLC Novaya Clinica
  • Saint Petersburg, Russia, 196603
    • Private Medical Institution Euromedservice
  • Saint Petersburg, Russia, 197758
    • Russian Scientific Center of Radiology and Surgical Technologies
  • Tambov, Russia, 392013
    • Tambov Regional Oncology Clinical Dispansary
  • Tyumen, Russia, 625041
    • Multifunctional clinical medical center 'Medical city'
• South Korea
  • Daejeon, South Korea, 35015
    • Chungnam national university hospital
  • Gwangju, South Korea, 61469
    • Chonnam National University Hospital
  • Gyeonggi-do, South Korea, 16247
    • The Catholic university of Korea, St. Vincent's Hospital
  • Seoul, South Korea, 03080
    • Seoul National University Hospital
  • Seoul, South Korea, 05505
    • Asan Medical Center
  • Seoul, South Korea, 03722
    • Severance Hospital Yonsei University Health System
  • Seoul, South Korea, 03181
    • Kangbuk Samsung Hospital
  • Seoul, South Korea, 06591
    • The Catholic University of Korea Seoul St Marys Hospital
  • Seoul, South Korea, 07061
    • Seoul Metropolitan Government Seoul National University Boramae Medical Center
  • Yangsan, South Korea, 50612
    • Pusan National University Yangsan Hospital
• Spain
  • Barcelona, Spain, 08003
    • Hosp. Del Mar
  • Barcelona, Spain, 08036
    • Hosp Clinic de Barcelona
  • Madrid, Spain, 28040
    • Hosp. Clinico San Carlos
  • Madrid, Spain, 28034
    • Hosp. Univ. Ramon Y Cajal
  • Madrid, Spain, 28050
    • Hosp Univ Fund Jimenez Diaz
  • Madrid, Spain, 28050
    • Hosp Univ Hm Sanchinarro
  • Málaga, Spain, 29010
    • Hosp Virgen de La Victoria
  • Ourense, Spain, 32005
    • Complexo Hosp. Univ. de Ourense
  • Pontevedra, Spain, 36204
    • Complejo Hospitalario de Vigo
  • Pozuelo de Alarcón, Spain, 28223
    • Hosp. Quiron Madrid Pozuelo
  • Sabadell, Spain, 08208
    • Corporacio Sanitari Parc Tauli
  • Santander, Spain, 39008
    • Hosp. Univ. Marques de Valdecilla
  • Santiago de Compostela, Spain, 15706
    • H. Clinico Universitario de Santiago de Compostela
  • Seville, Spain, 41013
    • Hosp. Virgen Del Rocio
  • Seville, Spain, 41009
    • Hosp. Virgen Macarena
  • Valencia, Spain, 46009
    • Instituto Valenciano de Oncologia
  • Valencia, Spain, 46010
    • Hosp. Clinico Univ. de Valencia
• Taiwan
  • Kaohsiung City, Taiwan, 83301
    • Kaohsiung Chang Gung Memorial Hospital
  • Kaohsiung City, Taiwan, 807
    • Kaohsiung Medical University Chung Ho Memorial Hospital
  • Taichung, Taiwan, 40447
    • China Medical University Hospital
  • Tainan, Taiwan, 70403
    • National Cheng Kung University Hospital
  • Taipei, Taiwan, 10002
    • National Taiwan University Hospital
  • Taoyuan District, Taiwan, 333
    • Chang-Gung Memorial Hospital, LinKou Branch
• Turkey (Türkiye)
  • Adana, Turkey (Türkiye), 1130
    • Adana Acibadem Hospital
  • Ankara, Turkey (Türkiye), 06520
    • Memorial Ankara Hastanesi
  • Ankara, Turkey (Türkiye), 6100
    • Hacettepe University Medical Faculty
  • Ankara, Turkey (Türkiye), 6200
    • Dr Abdurrahman Yurtaslan Oncology Training and Research Hospital
  • Aydin, Turkey (Türkiye), 09100
    • Adnan Menderes University Training and Research Hospital
  • Edirne, Turkey (Türkiye), 22030
    • Trakya University Medical Faculty
  • Istanbul, Turkey (Türkiye), 34096
    • Istanbul University Cerrahpasa Medical Faculty
  • Istanbul, Turkey (Türkiye), 34732
    • Istanbul Medeniyet University Goztepe Training and Research Hospital
  • Izmir, Turkey (Türkiye), 35100
    • Ege University
  • Kocaeli, Turkey (Türkiye)
    • Kocaeli University Medical Faculty
  • Konya, Turkey (Türkiye), 42080
    • Necmettin Erbakan University Meram Medical Faculty
  • Trabzon, Turkey (Türkiye), 61080
    • Karadeniz Teknik University Medical Faculty
• United Kingdom
  • Lancaster, United Kingdom, LA1 4RP
    • Royal Lancaster Infirmary
  • London, United Kingdom, EC1A 7BE
    • St Bartholomew'S Hospital
  • London, United Kingdom, NW1 2PG
    • University College London Hospitals Nhs Foundation Trust
  • Nottingham, United Kingdom, NG5 1PB
    • Nottingham University Hospitals NHS Trust
• United States
  • Colorado
    • Aurora, Colorado, United States, 80012
      • Rocky Mountain Cancer Centers
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Norton Cancer Institute
  • Maryland
    • Rockville, Maryland, United States, 20850
      • Maryland Oncology Hematology, PA
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Hackensack University Medical Center
  • New York
    • New York, New York, United States, 10021
      • Weill Cornell Medical College - NY Presbyterian Hospital
    • White Plains, New York, United States, 10601
      • White Plains Hospital Center for Cancer Care
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Levine Cancer Institute, Carolinas HealthCare System
  • Ohio
    • Toledo, Ohio, United States, 43623-3536
      • Toledo Clinic Cancer Centers
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Penn State Hershey Cancer Institute
  • Texas
    • Fort Worth, Texas, United States, 76104
      • Texas Oncology, P.A.
    • Houston, Texas, United States, 77030
      • The University of Texas MD Anderson Cancer Center
  • Virginia
    • Norfolk, Virginia, United States, 23502
      • Virginia Oncology Associates

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histologic demonstration of transitional cell carcinoma of the urothelium. Variant urothelial carcinoma histologies such as glandular or squamous differentiation, or evolution to more aggressive phenotypes such as sarcomatoid or micropapillary change are acceptable
• Metastatic or locally advanced urothelial cancer
• Must have measurable disease by radiological imaging according to the Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1) at baseline
• Prior systemic therapy for metastatic urothelial cancer: (a) For Phase 1b erdafitinib + cetrelimab cohort: Any number of lines of prior therapy; (b) For Phase 1b erdafitinib + cetrelimab + platinum chemotherapy cohort: No prior systemic therapy for metastatic disease; and renal function for participants must have a creatinine clearance (CrCl) greater than (>) 30 milliliter per minute (mL/min) to receive carboplatin and >60 mL/min to receive cisplatin as calculated by Cockcroft Gault and (c) Phase 2: No prior systemic therapy for metastatic disease and cisplatin-ineligible based on: ECOG PS 0-1 and at least one of the following criteria: Renal function defined as creatinine clearance (CrCl) less than (˂) 60 mL/min as calculated by Cockcroft-Gault; Grade 2 or higher peripheral neuropathy per NCI-CTCAE version 5.0; Grade 2 or higher hearing loss per NCI-CTCAE version 5.0 OR ECOG PS 2
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) grade of: (a) Phase 1b erdafitinib + cetrelimab cohort: ECOG 0-2; (b) Phase 1b erdafitinib + cetrelimab + platinum chemotherapy cohort: ECOG 0-1 for cisplatin and 0-2 for carboplatin (c) Phase 2: ECOG 0-2

Exclusion Criteria:

• Treatment with any other investigational agent or participation in another clinical study with therapeutic intent within 30 days prior to Cycle 1 Day 1. For Phase 1b, participants who have received the following prior antitumor therapy: received nitrosoureas and mitomycin C within 6 weeks
• Phase 1b erdafitinib + cetrelimab cohort: Chemotherapy within 3 weeks of Cycle 1 Day 1; Phase 1b erdafitinib + cetrelimab + platinum chemotherapy cohort and Phase 2: Prior neoadjuvant/adjuvant chemotherapy is allowed if the last dose was given >12 months prior to recurrent disease progression and did not result in drug-related toxicity leading to treatment discontinuation
• Prior anti-programmed death receptor-1 (PD-1), anti-programmed death ligand-1 (PD-L1), or anti-programmed death ligand-2 (PD-L2) therapy. Prior neoadjuvant/adjuvant checkpoint inhibitor therapy is allowed if the last dose was given more than (>)12 months prior to recurrent disease progression and did not result in drug-related toxicity leading to treatment discontinuation. PD-1 for non-muscle invasive bladder cancer is also allowed
• Active malignancies requiring concurrent therapy other than urothelial cancer
• Symptomatic central nervous system metastases

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 1b: Dose Escalation; Two dosing cohorts (erdafitinib and cetrelimab; and erdafitinib, cetrelimab and cisplatin/carboplatin) are explored in Phase 1b of the study. Participants will receive erdafitinib orally followed by cetrelimab intravenously (IV) and carboplatin/cisplatin IV as a part of platinum chemotherapy. The dose levels will be escalated sequentially based on the decisions of the Study Evaluation Team (SET) until the recommended Phase 2 Dose (RP2D) has been identified.	Drug: Erdafitinib; Participants will receive erdafitinib orally.; Other Names: JNJ-42756493; Drug: Cetrelimab; Participants will receive cetrelimab by intravenous infusion.; Other Names: JNJ-63723283; Drug: Cisplatin; Participants will receive cisplatin by intravenous infusion as a part of platinum chemotherapy.; Drug: Carboplatin; Participants will receive carboplatin by intravenous infusion as a part of platinum chemotherapy.
Experimental: Phase 2: Dose Expansion; The participants will be randomized in a 1:1 manner to receive either erdafitinib alone (orally) or the identified RP2D of Phase 1b for erdafitinib (orally) in combination with cetrelimab (IV).	Drug: Erdafitinib; Participants will receive erdafitinib orally.; Other Names: JNJ-42756493; Drug: Cetrelimab; Participants will receive cetrelimab by intravenous infusion.; Other Names: JNJ-63723283

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1b: Number of Participants With Dose-Limiting Toxicity (DLTs)	Number of participants with DLTs were reported. The DLTs as per National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI-CTCAE version 5.0) are specific adverse events defined as grade 3 (severe), grade 4 (life-threatening), and grade 5 (death) non-hematological toxicity or hematological toxicity.	Up to 8 weeks
Phase 2: Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 by Investigator Assessment	ORR is defined as the percentage of participants who achieved confirmed complete response (CR) or confirmed partial response (PR), according to response evaluation criteria in solid tumors (RECIST) version1.1. As per RECIST version 1.1, CR: disappearance of all lesions; all lymph nodes were non-pathological in size and normalization of tumor marker level; PR: greater than or equal to (>=) 30 percent (%) decrease in the sum of the diameters of all target lesions compared with baseline, in absence of new lesions or unequivocal progression of nontarget lesions.	From Day 1 up to 36 months
Phase 2: Number of Participants With Treatment-emergent Adverse Event (TEAEs)	Number of participants with TEAEs were reported. An adverse event is any untoward medical event that occurs in a participant administered an investigational product and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. TEAEs were defined as adverse events with onset or worsening on or after date of first dose of study treatment.	From Day 1 up to 36 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Phase 1b and Phase 2: Plasma Concentration of Erdafitinib	Up to 6 years 1 month
Phase 1b and Phase 2: Serum Concentration of Cetrelimab	Up to 6 years 1 month
Phase 1b: Plasma Concentration of Platinum (Cisplatin and Carboplatin) Chemotherapy	Up to 6 years 1 month
Phase 1b and Phase 2: Number of Participants With Anti-Cetrelimab Antibodies	Up to 6 years 1 month
Phase 2: Number of Participants With Serious Adverse Events (SAEs)	Up to 6 years 1 month
Phase 2: Number of Participants With Abnormal Laboratory Values	Up to 6 years 1 month
Phase 2: Duration of Response (DoR)	Up to 6 years 1 month
Phase 2: Time to Response (TTR)	Up to 6 years 1 month
Phase 2: Progression-free Survival (PFS)	Up to 6 years 1 month
Phase 2: Overall Survival (OS)	Up to 6 years 1 month

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC
• Investigators: Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC

Publications and helpful links

General Publications

• LaRoche JK, Lanier J, Alvarenga R, Collins M, Costelloe T, Chiau A, Whetherly H, De Soete W, Faludi J, Rens K. Climate footprint of industry-sponsored in-human clinical trials: life cycle assessments of clinical trials spanning multiple phases and disease areas. BMJ Open. 2025 Feb 19;15(2):e085364. doi: 10.1136/bmjopen-2024-085364.
• Loriot Y, Powles T, Moreno V, Kang TW, Cicin I, Girvin A, Akapame S, O'Hagan A, Zhu W, Tammaro M, Thomas S, Triantos S, Siefker-Radtke AO. Erdafitinib or Erdafitinib Plus Cetrelimab for Patients With Metastatic Urothelial Carcinoma and FGFR Alterations: Final Results From the Phase II NORSE Study. J Clin Oncol. 2026 Mar 10;44(8):676-684. doi: 10.1200/JCO-25-00826. Epub 2026 Jan 15.

Study record dates

Study Major Dates

• Study Start (Actual): April 5, 2018
• Primary Completion (Actual): September 30, 2022
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: March 14, 2018
• First Submitted That Met QC Criteria: March 21, 2018
• First Posted (Actual): March 22, 2018

Study Record Updates

• Last Update Posted (Actual): March 30, 2026
• Last Update Submitted That Met QC Criteria: March 16, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Carcinoma; Carcinoma, Transitional Cell; Organic Chemicals; Inorganic Chemicals; Chlorine Compounds; Nitrogen Compounds; Coordination Complexes; Platinum Compounds; Carboplatin; Cisplatin; erdafitinib
• Other Study ID Numbers: CR108445; 2017-001980-19 (EudraCT Number); 42756493BLC2002 (Other Identifier: Janssen Research & Development, LLC); 2023-510295-31-00 (Registry Identifier: EUCT number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No