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

NCT03473743 | Active Not Recruiting Phase 1 Results FDA Drug

• 4 other identifiers: CR10844542756493BLC20022017-001980-192023-510295-31-00
• Study Type: interventional
• Target: 125
• Locations: 12 countries
• Sites: 120

Brief Summary

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.

Conditions

Urothelial Carcinoma

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (10)

• 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

Study Arms (2)

Phase 1b: Dose Escalation

EXPERIMENTAL

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; Drug: Cetrelimab; Drug: Cisplatin; Drug: Carboplatin

Phase 2: Dose Expansion

EXPERIMENTAL

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; Drug: Cetrelimab

Interventions

Cetrelimab DRUG

Participants will receive cetrelimab by intravenous infusion.

Also known as: JNJ-63723283

Phase 1b: Dose Escalation; Phase 2: Dose Expansion

Cisplatin DRUG

Participants will receive cisplatin by intravenous infusion as a part of platinum chemotherapy.

Phase 1b: Dose Escalation

Carboplatin DRUG

Participants will receive carboplatin by intravenous infusion as a part of platinum chemotherapy.

Phase 1b: Dose Escalation

Erdafitinib DRUG

Participants will receive erdafitinib orally.

Also known as: JNJ-42756493

Phase 1b: Dose Escalation; Phase 2: Dose Expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (127)

Rocky Mountain Cancer Centers

Aurora, Colorado, 80012, United States

Location

Norton Cancer Institute

Louisville, Kentucky, 40202, United States

Location

Maryland Oncology Hematology, PA

Rockville, Maryland, 20850, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Weill Cornell Medical College - NY Presbyterian Hospital

New York, New York, 10021, United States

Location

White Plains Hospital Center for Cancer Care

White Plains, New York, 10601, United States

Location

Levine Cancer Institute, Carolinas HealthCare System

Charlotte, North Carolina, 28204, United States

Location

Toledo Clinic Cancer Centers

Toledo, Ohio, 43623-3536, United States

Location

Penn State Hershey Cancer Institute

Hershey, Pennsylvania, 17033, United States

Location

Texas Oncology, P.A.

Fort Worth, Texas, 76104, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Virginia Oncology Associates

Norfolk, Virginia, 23502, United States

Location

Brest Regional Oncology Dispensary

Brest, 224027, Belarus

Location

Grodno University Hospital

Grodno, 230017, Belarus

Location

Gomel Regional Clinical Oncology Dispensary

Homyel, 246012, Belarus

Location

State Institution N.N. Alexandrov Republican Scientific and

Lesnoy, 223040, Belarus

Location

Minsk city Clinical Oncological Dispensary

Minsk, 220013, Belarus

Location

Mogilev Regional Hospital

Mogilev, 212018, Belarus

Location

Vitebsk Regional Clinical Hospital

Vitebsk, 210603, Belarus

Location

ULB Hôpital Erasme

Brussels, 1070, Belgium

Location

Cliniques Universitaires Saint Luc

Brussels, 1200, Belgium

Location

Jolimont

Haine-Saint-Paul, 7100, Belgium

Location

Az Groeninge

Kortrijk, 8500, Belgium

Location

CHU de Liège - Domaine Universitaire du Sart Tilman

Liège, 4000, Belgium

Location

AZ Nikolaas - Campus Sint-Niklaas Moerland

Sint-Niklaas, 9100, Belgium

Location

GZA Ziekenhuizen- Campus St Augustinus

Wilrijk, 2610, Belgium

Location

Fundacao Pio XII

Barretos, 14784-400, Brazil

Location

Santa Casa de Misericordia de Belo Horizonte

Belo Horizonte, 30150-221, Brazil

Location

Liga Paranaense de Combate ao Cancer

Curitiba, 81520 060, Brazil

Location

Oncocentro Servicos Medicos e Hospitalares Ltda - Oncocentro

Fortaleza, 60170-170, Brazil

Location

Oncoclinicas Rio de Janeiro S A

Rio de Janeiro, 22250 905, Brazil

Location

Instituto de Educacao, Pesquisa e Gestao em Saude Instituto Americas (COI)

Rio de Janeiro, 22775 001, Brazil

Location

CEPHO Centro de Estudos e Pesquisa de Hematologia e Oncologia

Santo André, 09060-650, Brazil

Location

Institut de Cancerologie de Ouest (ICO) Site Paul Papin

Angers, 49055, France

Location

Hopital Saint André

Bordeaux, 33075, France

Location

Centre Francois Baclesse

Caen, 14000, France

Location

Centre hospitalier Saint Louis

La Rochelle, 17019, France

Location

Centre Leon Berard

Lyon, 69008, France

Location

APHM Hopital Timone

Marseille, 13005, France

Location

Hopital Europeen Georges Pompidou

Paris, 75015, France

Location

Clinique Sainte Anne

Strasbourg, 67000, France

Location

CHRU de Tours

Tours, 37044, France

Location

Institut de Cancerologie de Lorraine

Vandœuvre-lès-Nancy, 54519, France

Location

Institut Gustave Roussy

Villejuif, 94800, France

Location

Cliniche Humanitas Gavazzeni

Bergamo, 24125, Italy

Location

Istituto di Candiolo, IRCCS

Candiolo, 10060, Italy

Location

Ospedale Di Zona B Ramazzini

Carpi, 41012, Italy

Location

UOS Oncologia Medica, A.O. Cannizzaro

Catania, 95126, Italy

Location

Arcispedale S. Anna Ferrara

Ferrara, 44124, Italy

Location

PO A.Manzoni di Lecco, ASST Lecco - Oncologia Medica - Lecco

Lecco, 23900, Italy

Location

Ospedale Civile Di Livorno

Livorno, 57122, Italy

Location

IRCCS Ospedale San Raffaele

Milan, 20132, Italy

Location

ASST Grande Ospedale Metropolitano Niguarda

Milan, 20162, Italy

Location

Ospedale S. Maria Della Misericordia Centro Operativo Studi Clinici SC Oncologia Medica

Perugia, 06132, Italy

Location

AUSL DI PIACENZA - Ospedale Guglielmo da Saliceto

Piacenza, 29121, Italy

Location

Campus Bio Medico di Roma

Roma, 00128, Italy

Location

Azienda Socio Sanitaria Territoriale (ASST) della Valtellin

Sondrio, 23100, Italy

Location

Azienda Ospedaliera S. Maria Terni

Terni, 05100, Italy

Location

Azienda Ospedaliero Universitaria S.Maria Della Misericordia

Udine, 33100, Italy

Location

Przychodnia Lekarska KOMED Roman Karaszewski

Konin, 62-500, Poland

Location

Wojewodzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im M Kopernika w Lodzi

Lodz, 93 513, Poland

Location

LUX MED Onkologia Sp. z o.o.

Warsaw, 01-748, Poland

Location

Centralny Szpital Kliniczny MSWiA w Warszawie

Warsaw, 02-507, Poland

Location

Altai Regional Oncology Dispensary

Barnaul, 656049, Russia

Location

Ivanovo Regional Oncology Dispensary

Ivanovo, 153040, Russia

Location

GUZ Kursk Regional Oncology Dispensary

Kislino Village, 305524, Russia

Location

Leningrad Regional Oncology Dispensary

Kuzmolovsky, 188663, Russia

Location

City Clinical Hospital n.a. D.D.Pletnev

Moscow, 105077, Russia

Location

Russian Scientific Center of Roentgenoradiology

Moscow, 117997, Russia

Location

Moscow City Clinical Hospital # 62

Moscow, 125130, Russia

Location

Clinical Diagnostic Centre of Nizhny Novgorod Region

Nizhny Novgorod, 603000, Russia

Location

Privolzhsky District Medical Centre

Nizhny Novgorod, 603074, Russia

Location

Clinical Oncology Dispensary

Omsk, 644013, Russia

Location

LLC Novaya Clinica

Pyatigorsk, 357500, Russia

Location

Private Medical Institution Euromedservice

Saint Petersburg, 196603, Russia

Location

Russian Scientific Center of Radiology and Surgical Technologies

Saint Petersburg, 197758, Russia

Location

Tambov Regional Oncology Clinical Dispansary

Tambov, 392013, Russia

Location

Multifunctional clinical medical center 'Medical city'

Tyumen, 625041, Russia

Location

Chungnam National University Hospital

Daejeon, 35015, South Korea

Location

Chonnam National University Hospital

Gwangju, 61469, South Korea

Location

The Catholic university of Korea, St. Vincent's Hospital

Gyeonggi-do, 16247, South Korea

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Kangbuk Samsung Hospital

Seoul, 03181, South Korea

Location

Severance Hospital Yonsei University Health System

Seoul, 03722, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

The Catholic University of Korea Seoul St Marys Hospital

Seoul, 06591, South Korea

Location

Seoul Metropolitan Government Seoul National University Boramae Medical Center

Seoul, 07061, South Korea

Location

Pusan National University Yangsan Hospital

Yangsan, 50612, South Korea

Location

Hosp. Del Mar

Barcelona, 08003, Spain

Location

Hosp Clinic de Barcelona

Barcelona, 08036, Spain

Location

Hosp. Univ. Ramon Y Cajal

Madrid, 28034, Spain

Location

Hosp. Clinico San Carlos

Madrid, 28040, Spain

Location

Hosp Univ Fund Jimenez Diaz

Madrid, 28050, Spain

Location

Hosp Univ Hm Sanchinarro

Madrid, 28050, Spain

Location

Hosp Virgen de La Victoria

Málaga, 29010, Spain

Location

Complexo Hosp. Univ. de Ourense

Ourense, 32005, Spain

Location

Complejo Hospitalario de Vigo

Pontevedra, 36204, Spain

Location

Hosp. Quiron Madrid Pozuelo

Pozuelo de Alarcón, 28223, Spain

Location

Corporacio Sanitari Parc Tauli

Sabadell, 08208, Spain

Location

Hosp. Univ. Marques de Valdecilla

Santander, 39008, Spain

Location

H. Clinico Universitario de Santiago de Compostela

Santiago de Compostela, 15706, Spain

Location

Hosp. Virgen Macarena

Seville, 41009, Spain

Location

Hosp. Virgen Del Rocio

Seville, 41013, Spain

Location

Instituto Valenciano de Oncologia

Valencia, 46009, Spain

Location

Hosp. Clinico Univ. de Valencia

Valencia, 46010, Spain

Location

Kaohsiung Medical University Chung Ho Memorial Hospital

Kaohsiung City, 807, Taiwan

Location

Kaohsiung Chang Gung Memorial Hospital

Kaohsiung City, 83301, Taiwan

Location

China Medical University Hospital

Taichung, 40447, Taiwan

Location

National Cheng Kung University Hospital

Tainan, 70403, Taiwan

Location

National Taiwan University Hospital

Taipei, 10002, Taiwan

Location

Chang-Gung Memorial Hospital, LinKou Branch

Taoyuan District, 333, Taiwan

Location

Adana Acibadem Hospital

Adana, 1130, Turkey (Türkiye)

Location

Memorial Ankara Hastanesi

Ankara, 06520, Turkey (Türkiye)

Location

Hacettepe University Medical Faculty

Ankara, 6100, Turkey (Türkiye)

Location

Dr Abdurrahman Yurtaslan Oncology Training and Research Hospital

Ankara, 6200, Turkey (Türkiye)

Location

Adnan Menderes University Training and Research Hospital

Aydin, 09100, Turkey (Türkiye)

Location

Trakya University Medical Faculty

Edirne, 22030, Turkey (Türkiye)

Location

Istanbul University Cerrahpasa Medical Faculty

Istanbul, 34096, Turkey (Türkiye)

Location

Istanbul Medeniyet University Goztepe Training and Research Hospital

Istanbul, 34732, Turkey (Türkiye)

Location

Ege University

Izmir, 35100, Turkey (Türkiye)

Location

Kocaeli University Medical Faculty

Kocaeli, Turkey (Türkiye)

Location

Necmettin Erbakan University Meram Medical Faculty

Konya, 42080, Turkey (Türkiye)

Location

Karadeniz Teknik University Medical Faculty

Trabzon, 61080, Turkey (Türkiye)

Location

Royal Lancaster Infirmary

Lancaster, LA1 4rp, United Kingdom

Location

St Bartholomew's Hospital

London, EC1A 7BE, United Kingdom

Location

University College London Hospitals Nhs Foundation Trust

London, NW1 2PG, United Kingdom

Location

Nottingham University Hospitals NHS Trust

Nottingham, NG5 1PB, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 41538748 DERIVED

• 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.

  PMID: 39971605 DERIVED

MeSH Terms

Conditions

Carcinoma, Transitional Cell

Interventions

erdafitinib; Cisplatin; Carboplatin

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Coordination Complexes; Organic Chemicals

Results Point of Contact

• Title: Executive Medical Director
• Organization: Janssen Research & Development, LLC

ClinicalTrialDisclosure@its.jnj.com

844-434-4210

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: March 14, 2018
• First Posted: March 22, 2018
• Study Start: April 5, 2018
• Primary Completion: September 30, 2022
• Study Completion (Estimated): December 31, 2026
• Last Updated: March 30, 2026
• Results First Posted: October 25, 2023

Record last verified: 2026-03

Locations

RU (15); FR (11); BE (7); ES (17); US (12); IT (15); PL (4); TU (12); GB (4); BR (7); KR (10); TW (6)