A Phase 1b-2 Study to Evaluate Safety, Efficacy, Pharmacokinetics, and Pharmacodynamics of Erdafitinib Plus JNJ-63723283, an Anti-PD-1 Monoclonal Antibody, in Subjects With Metastatic or Surgically Unresectable Urothelial Cancer With Selected FGFR Gene Al

Condition: Urothelial Carcinoma

Intervention:

• Drug: Erdafitinib
• Drug: Cetrelimab

Purpose: The purpose of this study is to identify the recommended Phase 2 dose (RP2D) and schedule of erdafitinib in combination with cetrelimab (Phase 1b) and to evaluate the safety and clinical activity of erdafitinib alone and in combination with cetrelimab in first line metastatic urothelial carcinoma (mUC) setting (Phase 2).

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03473743

Sponsor: Janssen Research & Development, LLC

Primary Outcome Measures:

• Measure: Phase 1b: Percentage of Participants with Dose-Limiting Toxicity (DLT)
• Time Frame: Approximately up to 8 weeks
• Safety Issue:
• Measure: Phase 1b: Number of Participants with Adverse Events (AEs)
• Time Frame: Approximately up to 2 years
• Safety Issue:
• Measure: Phase 2: Overall Response Rate (ORR) (Partial Response [PR] or Better) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 by Investigator Assessment
• Time Frame: Approximately up to 2 years
• Safety Issue:
• Measure: Phase 2: Number of Participants with AEs
• Time Frame: Approximately up to 2 years
• Safety Issue:

Secondary Outcome Measures:

• Measure: Phase 1b and Phase 2: Plasma Concentration of Erdafitinib
• Time Frame: Cycle(C)1 Day(D)1 up to C3D1 (each cycle of 28 days)
• Safety Issue:
• Measure: Phase 1b and Phase 2: Serum Concentration of Cetrelimab
• Time Frame: Up to Follow-up (approximately up to 2 years)
• Safety Issue:
• Measure: Phase 1b and Phase 2: Number of Participants with Anti-Cetrelimab Antibodies
• Time Frame: Up to Follow-up (approximately up to 2 years)
• Safety Issue:
• Measure: Phase 2: Number of Participants with Serious Adverse Events (SAEs)
• Time Frame: Approximately up to 2 years
• Safety Issue:
• Measure: Phase 2: Number of Participants with Abnormal Laboratory Values
• Time Frame: Approximately up to 2 years
• Safety Issue:
• Measure: Phase 2: Duration of Response (DoR)
• Time Frame: Approximately up to 2 years
• Safety Issue:
• Measure: Phase 2: Time to Response (TTR)
• Time Frame: Approximately up to 2 years
• Safety Issue:
• Measure: Phase 2: Progression-Free Survival (PFS)
• Time Frame: Approximately up to 2 years
• Safety Issue:
• Measure: Phase 2: Overall Survival (OS)
• Time Frame: Approximately up to 2 years
• Safety Issue:

Estimated Enrollment: 150

Study Start Date: April 5, 2018

Phase: Phase 1/Phase 2

Eligibility:

• Age: minimum 18 Years maximum N/A
• Gender: All

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) Phase 1b: Any number of lines of prior therapy; (b) Phase 2: No prior systemic therapy for metastatic disease and cisplatin-ineligible
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) grade of: 0, 1, or 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
• Chemotherapy within 3 weeks of Cycle 1 Day 1
• 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
• Active malignancies requiring concurrent therapy other than urothelial cancer
• Symptomatic central nervous system metastases

Contact:

• Study Contact
• 844-434-4210

Locations:

• Rocky Mountain Cancer Centers
• Aurora Colorado 80012 United States

• Norton Cancer Institute
• Louisville Kentucky 40202 United States

• Maryland Oncology Hematology, PA
• Rockville Maryland 20850 United States

• Nevada Cancer Institute
• Las Vegas Nevada 89169 United States

• Hackensack University Medical Center
• Hackensack New Jersey 07601 United States

• Weill Cornell Medical College – NY Presbyterian Hospital
• New York New York 10021 United States

• White Plains Hospital Center for Cancer Care
• White Plains New York 10601 United States

• Levine Cancer Institute, Carolinas HealthCare System
• Charlotte North Carolina 28204 United States

• Toledo Clinic Cancer Centers
• Toledo Ohio 43623-3536 United States

• St. Luke’s University Health Network
• Bethlehem Pennsylvania 18015 United States

• Penn State Hershey Cancer Institute
• Hershey Pennsylvania 17033 United States

• Texas Oncology, P.A.
• Fort Worth Texas 76104 United States

• The University of Texas MD Anderson Cancer Center
• Houston Texas 77030 United States

• The University of Texas MD Anderson Cancer Center
• San Antonio Texas 78229-3931 United States

• University of Oklahoma Health Sciences Center
• San Antonio Texas 78229 United States

• Virginia Oncology Associates
• Norfolk Virginia 23502 United States

• Cliniques Universitaires Saint-Luc
• Brussel 1200 Belgium

• ULB Hôpital Erasme
• Bruxelles 1070 Belgium

• Jolimont
• Haine-Saint-Paul, La Louviere 7100 Belgium

• Az Groeninge
• Kortrijk 8500 Belgium

• CHU de Liège – Domaine Universitaire du Sart Tilman
• Liege 4000 Belgium

• AZ Nikolaas – Campus Sint-Niklaas Moerland
• Sint-Niklaas 9100 Belgium

• GZA Ziekenhuizen- Campus St Augustinus
• Wilrijk 2610 Belgium

• Institut de Cancerologie de Ouest (ICO) Site Paul Papin
• Angers Cedex 02 49055 France

• Hopital Saint André
• Bordeaux 33075 France

• Centre Francois Baclesse
• Caen 14000 France

• Centre Hospitalier Départemental VENDEE
• La Roche Sur Yon 85925 France

• Centre hospitalier Saint Louis
• La Rochelle Cedex 1 17019 France

• Centre Leon Bérard
• Lyon 69008 France

• APHM Hopital Timone
• Marseille 13005 France

• Hôpital Européen Georges Pompidou
• Paris 75015 France

• Centre Hospitalier Universitaire de Reims, Hôpital Robert Debré
• Reims 51092 France

• Clinique Sainte Anne
• Strasbourg 67000 France

• Institut Universitaire du Cancer Toulouse Oncopole
• Toulouse 31000 France

• CHRU de Tours
• Tours 37044 France

• Institut de Cancérologie de Lorraine
• Vandoeuvre lès Nancy 54519 France

• Institut Gustave Roussy
• Villejuif 94800 France

• LTD ‘Aversi Clinic’
• T’bilisi 0160 Georgia

• Institute for Personalized Medicine LTD
• Tbilisi 0186 Georgia

• Research Institute of Clinical Medicine
• Tbilisi 112 Georgia

• LTD Mammological Center Named after K Madichi
• Tblisi 0159 Georgia

• Cliniche Humanitas Gavazzeni
• Bergamo 24125 Italy

• Policlinico Universitario Di Cagliari
• Cagliari 09134 Italy

• Istituto di Candiolo, IRCCS
• Candiolo 10060 Italy

• Ospedale Di Zona B Ramazzini
• Carpi 41012 Italy

• UOS Oncologia Medica, A.O. Cannizzaro
• Catania 95126 Italy

• P.O. Ss. Annunziata
• Chieti Scalo 66013 Italy

• Arcispedale S. Anna Ferrara
• Ferrara 44124 Italy

• PO A.Manzoni di Lecco, ASST Lecco – Oncologia Medica – Lecco
• Lecco 23900 Italy

• IRCCS Ospedale San Raffaele
• Milano 20132 Italy

• ASST Grande Ospedale Metropolitano Niguarda
• Milano 20162 Italy

• Ospedale S. Maria Della Misericordia Centro Operativo Studi Clinici SC Oncologia Medica
• Perugia 06132 Italy

• AUSL DI PIACENZA – Ospedale Guglielmo da Saliceto
• Piacenza 29121 Italy

• Azienda USL Toscana Nord Ovest
• Pontedera (PI) 56025 Italy

• Arcispedale Santa Maria Nuova – IRCCS
• Reggio Emilia 42123 Italy

• Campus Bio-Medico di Roma
• Roma 00128 Italy

• PO Ospedale S.Anna, ASST Lariana
• San Fermo della Battaglia 22042 Italy

• Azienda Socio Sanitaria Territoriale (ASST) della Valtellin
• Sondrio 23100 Italy

• Azienda Ospedaliera S. Maria Terni
• Terni 05100 Italy

• Azienda Ospedaliero Universitaria S.Maria Della Misericordia
• Udine 33100 Italy

• Chonnam National University Hospital
• Gwangju 61469 Korea, Republic of

• Chonnam National University Hwasun Hospital
• Jeonnam 58128 Korea, Republic of

• CHA Bundang Medical center, CHA University
• Seongnam 13496 Korea, Republic of

• Seoul National University Hospital
• Seoul 03080 Korea, Republic of

• Kangbuk Samsung Hospital
• Seoul 03181 Korea, Republic of

• Severance Hospital
• Seoul 03722 Korea, Republic of

• Asan Medical Center
• Seoul 05505 Korea, Republic of

• The Catholic University of Korea, Seoul St.Mary’s Hospital
• Seoul 06591 Korea, Republic of

• SMG – SNU Boramae Medical Center
• Seoul 07061 Korea, Republic of

• The Catholic University of Korea St. Vincent’s Hospital
• Suwon-si 16247 Korea, Republic of

• Pusan National University Yangsan Hospital
• Yangsan 50612 Korea, Republic of

• Altai Regional Oncology Dispensary
• Barnaul 656049 Russian Federation

• Ivanovo Regional Oncology Dispensary
• Ivanovo 153040 Russian Federation

• GUZ Kursk Regional Oncology Dispensary
• Kislino Village, Ryshkovsky Ru 305524 Russian Federation

• Leningrad Regional Oncology Dispensary
• Kuzmolovsky 188663 Russian Federation

• City Clinical Hospital n.a. D.D.Pletnev
• Moscow 105077 Russian Federation

• Russian Scientific Center of Roentgenoradiology
• Moscow 117997 Russian Federation

• Moscow City Clinical Hospital # 62
• Moscow 125130 Russian Federation

• Privolzhsky District Medical Centre
• Nizhny Novgorod 603074 Russian Federation

• Clinical Oncology Dispensary
• Omsk 644013 Russian Federation

• LLC Novaya Clinica
• Pyatigorsk 357500 Russian Federation

• Clinical Hospital #122 n.a. after L.G. Sokolov
• Saint Petersburg 194291 Russian Federation

• City Polyprofiled Hospital #2
• Saint Petersburg 194354 Russian Federation

• Private Medical Institution Euromedservice
• Saint Petersburg 196603 Russian Federation

• Clinical and research Oncological Center
• Saint Petersburg 197758 Russian Federation

• Russian Scientific Center of Radiology and Surgical Technologies
• Saint-Petersburg 197758 Russian Federation

• City Pokrovskaya Hospital
• St Petersburg 199106 Russian Federation

• Tambov Regional Oncology Clinical Dispansary
• Tambov 392013 Russian Federation

• Multifunctional clinical medical center ‘Medical city’
• Tyumen 625041 Russian Federation

• GBUZ ‘Regional clinical oncologic dispensary of Volgograd’
• Volgograd 400138 Russian Federation

• Hosp. Del Mar
• Barcelona 08003 Spain

• Hosp. Clinic I Provincial de Barcelona
• Barcelona 08036 Spain

• Hosp. Univ. Ramon Y Cajal
• Madrid 28034 Spain

• Hosp. Clinico San Carlos
• Madrid 28040 Spain

• Hosp. Univ. Fund. Jimenez Diaz
• Madrid 28050 Spain

• Hosp. Univ. Hm Sanchinarro
• Madrid 28050 Spain

• Hosp. Virgen de La Victoria
• Málaga 29010 Spain

• Complexo Hosp. Univ. de Ourense
• Ourense 32005 Spain

• Complejo Hospitalario de Vigo
• Pontevedra 36204 Spain

• Hosp. Quiron Madrid Pozuelo
• Pozuelo de Alarcon 28223 Spain

• Corporacio Sanitari Parc Tauli
• Sabadell 08208 Spain

• Hosp. Univ. Marques de Valdecilla
• Santander 39008 Spain

• H. Clinico Universitario de Santiago de Compostela
• Santiago de Compostela 15706 Spain

• Hosp. Virgen Macarena
• Sevilla 41009 Spain

• Hosp. Virgen Del Rocio
• Sevilla 41013 Spain

• Instituto Valenciano de Oncologia
• Valencia 46009 Spain

• Addenbrooke’s Hospital
• Cambridge CB2 0QQ United Kingdom

• Colchester Hospital University NHS
• Colchester CO4 5JL United Kingdom

• Royal Lancaster Infirmary
• Lancaster LA1 4rp United Kingdom

• St Bartholomew’s Hospital
• London EC1A 7BE United Kingdom

• University College London Hospitals Nhs Foundation Trust / Division Of Gi Services
• London NW1 2PG United Kingdom

• Kings College London at Guy’s Hospital
• London W1G 6AD United Kingdom

• Nottingham University Hospitals NHS Trust
• Nottingham NG5 1PB United Kingdom

View trial on ClinicalTrials.gov