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

NCT ID: NCT03473743

Last Updated: 2025-11-12

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 125 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-04-05
• Study Completion Date: 2026-12-31

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.

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.

Conditions

Urothelial Carcinoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Erdafitinib

Intervention Type: DRUG

Participants will receive erdafitinib orally.

Cetrelimab

Intervention Type: DRUG

Participants will receive cetrelimab by intravenous infusion.

Cisplatin

Intervention Type: DRUG

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

Carboplatin

Intervention Type: DRUG

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

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).

Group Type: EXPERIMENTAL

Erdafitinib

Intervention Type: DRUG

Participants will receive erdafitinib orally.

Cetrelimab

Intervention Type: DRUG

Participants will receive cetrelimab by intravenous infusion.

Interventions

Erdafitinib

Participants will receive erdafitinib orally.

Intervention Type: DRUG

Cetrelimab

Participants will receive cetrelimab by intravenous infusion.

Intervention Type: DRUG

Cisplatin

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

Intervention Type: DRUG

Carboplatin

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

Intervention Type: DRUG

Other Intervention Names

JNJ-42756493; JNJ-63723283

Eligibility Criteria

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

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

Sponsors

Janssen Research & Development, LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janssen Research & Development, LLC Clinical Trial

Role: STUDY_DIRECTOR

Janssen Research & Development, LLC

Locations

Rocky Mountain Cancer Centers

Aurora, Colorado, United States

Norton Cancer Institute

Louisville, Kentucky, United States

Maryland Oncology Hematology, PA

Rockville, Maryland, United States

Hackensack University Medical Center

Hackensack, New Jersey, United States

Weill Cornell Medical College - NY Presbyterian Hospital

New York, New York, United States

White Plains Hospital Center for Cancer Care

White Plains, New York, United States

Levine Cancer Institute, Carolinas HealthCare System

Charlotte, North Carolina, United States

Toledo Clinic Cancer Centers

Toledo, Ohio, United States

Penn State Hershey Cancer Institute

Hershey, Pennsylvania, United States

Texas Oncology, P.A.

Fort Worth, Texas, United States

The University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Virginia Oncology Associates

Norfolk, Virginia, United States

Brest Regional Oncology Dispensary

Brest, , Belarus

Grodno University Hospital

Grodno, , Belarus

Gomel Regional Clinical Oncology Dispensary

Homyel, , Belarus

State Institution N.N. Alexandrov Republican Scientific and

Lesnoy, , Belarus

Minsk city Clinical Oncological Dispensary

Minsk, , Belarus

Mogilev Regional Hospital

Mogilev, , Belarus

Vitebsk Regional Clinical Hospital

Vitebsk, , Belarus

ULB Hôpital Erasme

Brussels, , Belgium

Cliniques Universitaires Saint Luc

Brussels, , Belgium

Jolimont

Haine-Saint-Paul, , Belgium

Az Groeninge

Kortrijk, , Belgium

CHU de Liège - Domaine Universitaire du Sart Tilman

Liège, , Belgium

AZ Nikolaas - Campus Sint-Niklaas Moerland

Sint-Niklaas, , Belgium

GZA Ziekenhuizen- Campus St Augustinus

Wilrijk, , Belgium

Fundacao Pio XII

Barretos, , Brazil

Santa Casa de Misericordia de Belo Horizonte

Belo Horizonte, , Brazil

Liga Paranaense de Combate ao Cancer

Curitiba, , Brazil

Oncocentro Servicos Medicos e Hospitalares Ltda - Oncocentro

Fortaleza, , Brazil

Oncoclinicas Rio de Janeiro S A

Rio de Janeiro, , Brazil

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

Rio de Janeiro, , Brazil

CEPHO Centro de Estudos e Pesquisa de Hematologia e Oncologia

Santo André, , Brazil

Institut de Cancerologie de Ouest (ICO) Site Paul Papin

Angers, , France

Hopital Saint André

Bordeaux, , France

Centre Francois Baclesse

Caen, , France

Centre hospitalier Saint Louis

La Rochelle, , France

Centre Leon Berard

Lyon, , France

APHM Hopital Timone

Marseille, , France

Hopital Europeen Georges Pompidou

Paris, , France

Clinique Sainte Anne

Strasbourg, , France

CHRU de Tours

Tours, , France

Institut de Cancerologie de Lorraine

Vandœuvre-lès-Nancy, , France

Institut Gustave Roussy

Villejuif, , France

Cliniche Humanitas Gavazzeni

Bergamo, , Italy

Istituto di Candiolo, IRCCS

Candiolo, , Italy

Ospedale Di Zona B Ramazzini

Carpi, , Italy

UOS Oncologia Medica, A.O. Cannizzaro

Catania, , Italy

Arcispedale S. Anna Ferrara

Ferrara, , Italy

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

Lecco, , Italy

Ospedale Civile Di Livorno

Livorno, , Italy

IRCCS Ospedale San Raffaele

Milan, , Italy

ASST Grande Ospedale Metropolitano Niguarda

Milan, , Italy

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

Perugia, , Italy

AUSL DI PIACENZA - Ospedale Guglielmo da Saliceto

Piacenza, , Italy

Campus Bio Medico di Roma

Roma, , Italy

Azienda Socio Sanitaria Territoriale (ASST) della Valtellin

Sondrio, , Italy

Azienda Ospedaliera S. Maria Terni

Terni, , Italy

Azienda Ospedaliero Universitaria S.Maria Della Misericordia

Udine, , Italy

Przychodnia Lekarska KOMED Roman Karaszewski

Konin, , Poland

Wojewodzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im M Kopernika w Lodzi

Lodz, , Poland

LUX MED Onkologia Sp. z o.o.

Warsaw, , Poland

Centralny Szpital Kliniczny MSWiA w Warszawie

Warsaw, , Poland

Altai Regional Oncology Dispensary

Barnaul, , Russia

Ivanovo Regional Oncology Dispensary

Ivanovo, , Russia

GUZ Kursk Regional Oncology Dispensary

Kislino Village, , Russia

Leningrad Regional Oncology Dispensary

Kuzmolovsky, , Russia

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

Moscow, , Russia

Russian Scientific Center of Roentgenoradiology

Moscow, , Russia

Moscow City Clinical Hospital # 62

Moscow, , Russia

Clinical Diagnostic Centre of Nizhny Novgorod Region

Nizhny Novgorod, , Russia

Privolzhsky District Medical Centre

Nizhny Novgorod, , Russia

Clinical Oncology Dispensary

Omsk, , Russia

LLC Novaya Clinica

Pyatigorsk, , Russia

Private Medical Institution Euromedservice

Saint Petersburg, , Russia

Russian Scientific Center of Radiology and Surgical Technologies

Saint Petersburg, , Russia

Tambov Regional Oncology Clinical Dispansary

Tambov, , Russia

Multifunctional clinical medical center 'Medical city'

Tyumen, , Russia

Chungnam National University Hospital

Daejeon, , South Korea

Chonnam National University Hospital

Gwangju, , South Korea

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

Gyeonggi-do, , South Korea

Seoul National University Hospital

Seoul, , South Korea

Kangbuk Samsung Hospital

Seoul, , South Korea

Severance Hospital Yonsei University Health System

Seoul, , South Korea

Asan Medical Center

Seoul, , South Korea

The Catholic University of Korea Seoul St Marys Hospital

Seoul, , South Korea

Seoul Metropolitan Government Seoul National University Boramae Medical Center

Seoul, , South Korea

Pusan National University Yangsan Hospital

Yangsan, , South Korea

Hosp. Del Mar

Barcelona, , Spain

Hosp Clinic de Barcelona

Barcelona, , Spain

Hosp. Univ. Ramon Y Cajal

Madrid, , Spain

Hosp. Clinico San Carlos

Madrid, , Spain

Hosp Univ Fund Jimenez Diaz

Madrid, , Spain

Hosp Univ Hm Sanchinarro

Madrid, , Spain

Hosp Virgen de La Victoria

Málaga, , Spain

Complexo Hosp. Univ. de Ourense

Ourense, , Spain

Complejo Hospitalario de Vigo

Pontevedra, , Spain

Hosp. Quiron Madrid Pozuelo

Pozuelo de Alarcón, , Spain

Corporacio Sanitari Parc Tauli

Sabadell, , Spain

Hosp. Univ. Marques de Valdecilla

Santander, , Spain

H. Clinico Universitario de Santiago de Compostela

Santiago de Compostela, , Spain

Hosp. Virgen Macarena

Seville, , Spain

Hosp. Virgen Del Rocio

Seville, , Spain

Instituto Valenciano de Oncologia

Valencia, , Spain

Hosp. Clinico Univ. de Valencia

Valencia, , Spain

Kaohsiung Medical University Chung Ho Memorial Hospital

Kaohsiung City, , Taiwan

Kaohsiung Chang Gung Memorial Hospital

Kaohsiung City, , Taiwan

China Medical University Hospital

Taichung, , Taiwan

National Cheng Kung University Hospital

Tainan, , Taiwan

National Taiwan University Hospital

Taipei, , Taiwan

Chang-Gung Memorial Hospital, LinKou Branch

Taoyuan District, , Taiwan

Adana Acibadem Hospital

Adana, , Turkey (Türkiye)

Memorial Ankara Hastanesi

Ankara, , Turkey (Türkiye)

Hacettepe University Medical Faculty

Ankara, , Turkey (Türkiye)

Dr Abdurrahman Yurtaslan Oncology Training and Research Hospital

Ankara, , Turkey (Türkiye)

Adnan Menderes University Training and Research Hospital

Aydin, , Turkey (Türkiye)

Trakya University Medical Faculty

Edirne, , Turkey (Türkiye)

Istanbul University Cerrahpasa Medical Faculty

Istanbul, , Turkey (Türkiye)

Istanbul Medeniyet University Goztepe Training and Research Hospital

Istanbul, , Turkey (Türkiye)

Ege University

Izmir, , Turkey (Türkiye)

Kocaeli University Medical Faculty

Kocaeli, , Turkey (Türkiye)

Necmettin Erbakan University Meram Medical Faculty

Konya, , Turkey (Türkiye)

Karadeniz Teknik University Medical Faculty

Trabzon, , Turkey (Türkiye)

Royal Lancaster Infirmary

Lancaster, , United Kingdom

St Bartholomew's Hospital

London, , United Kingdom

University College London Hospitals Nhs Foundation Trust

London, , United Kingdom

Nottingham University Hospitals NHS Trust

Nottingham, , United Kingdom

Countries

Georgia; United States; Belarus; Belgium; Brazil; France; Italy; Poland; Russia; South Korea; Spain; Taiwan; Turkey (Türkiye); United Kingdom

References

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.

Reference Type: DERIVED

PMID: 39971605 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

42756493BLC2002

Identifier Type: OTHER

Identifier Source: secondary_id

2017-001980-19

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

2023-510295-31-00

Identifier Type: REGISTRY

Identifier Source: secondary_id

CR108445

Identifier Type: -

Identifier Source: org_study_id