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

Urothelial Carcinoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03473743
• Other study ID #: CR108445
• Secondary ID: 2017-001980-1942
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: April 5, 2018
• Est. completion date: June 30, 2025

Study information

• Verified date: June 2024
• Source: Janssen Research & Development, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 125
• Est. completion date: June 30, 2025
• Est. primary completion date: September 30, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Transitional Cell
• Urothelial Carcinoma

Intervention

Drug:
• Erdafitinib
Participants will receive erdafitinib orally.
• Cetrelimab
Participants will receive cetrelimab by intravenous infusion.
• Cisplatin
Participants will receive cisplatin by intravenous infusion as a part of platinum chemotherapy.
• Carboplatin
Participants will receive carboplatin by intravenous infusion as a part of platinum chemotherapy.

Locations

Country	Name	City	State
Belarus	Brest Regional Oncology Dispensary	Brest
Belarus	Gomel Regional Clinical Oncology Dispensary	Gomel
Belarus	Grodno University Hospital	Grodno
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
Belgium	Cliniques Universitaires Saint Luc	Bruxelles
Belgium	ULB Hôpital Erasme	Bruxelles
Belgium	Jolimont	Haine-Saint-Paul, La Louviere
Belgium	Az Groeninge	Kortrijk
Belgium	CHU de Liège - Domaine Universitaire du Sart Tilman	Liege
Belgium	AZ Nikolaas - Campus Sint-Niklaas Moerland	Sint-Niklaas
Belgium	GZA Ziekenhuizen- Campus St Augustinus	Wilrijk
Brazil	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	Instituto de Educacao, Pesquisa e Gestao em Saude Instituto Americas (COI)	Rio de Janeiro
Brazil	Oncoclinicas Rio de Janeiro S A	Rio de Janeiro
Brazil	CEPHO - Centro de Estudos e Pesquisa de Hematologia e Oncologia	Santo Andre
France	Institut de Cancerologie de Ouest (ICO) Site Paul Papin	Angers Cedex 02
France	Hopital Saint André	Bordeaux
France	Centre Francois Baclesse	Caen
France	Centre hospitalier Saint Louis	La Rochelle Cedex 1
France	Centre Leon Berard	Lyon
France	APHM Hopital Timone	Marseille
France	Hôpital Européen Georges Pompidou	Paris
France	Clinique Sainte Anne	Strasbourg
France	CHRU de Tours	Tours
France	Institut de Cancérologie de Lorraine	Vandoeuvre lès Nancy
France	Institut Gustave Roussy	Villejuif
Italy	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	ASST Grande Ospedale Metropolitano Niguarda	Milano
Italy	IRCCS Ospedale San Raffaele	Milano
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
Korea, Republic of	Chungnam National University Hospital	Daejeon
Korea, Republic of	Chonnam National University Hospital	Gwangju
Korea, Republic of	The Catholic university of Korea, St. Vincent's Hospital	Gyeonggi-do
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Kangbuk Samsung Hospital	Seoul
Korea, Republic of	Seoul Metropolitan Government Seoul National University Boramae Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Hospital Yonsei University Health System	Seoul
Korea, Republic of	The Catholic University of Korea Seoul St. Mary's Hospital	Seoul
Korea, Republic of	Pusan National University Yangsan Hospital	Yangsan-si
Poland	Przychodnia Lekarska KOMED Roman Karaszewski	Konin
Poland	Wojewodzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im M Kopernika w Lodzi	Lodz
Poland	Centralny Szpital Kliniczny MSWiA w Warszawie	Warszawa
Poland	LUX MED Onkologia Sp. z o.o.	Warszawa
Russian Federation	Altai Regional Oncology Dispensary	Barnaul
Russian Federation	Ivanovo Regional Oncology Dispensary	Ivanovo
Russian Federation	GUZ Kursk Regional Oncology Dispensary	Kislino Village, Ryshkovsky Ru
Russian Federation	Leningrad Regional Oncology Dispensary	Kuzmolovsky
Russian Federation	City Clinical Hospital n.a. D.D.Pletnev	Moscow
Russian Federation	Moscow City Clinical Hospital # 62	Moscow
Russian Federation	Russian Scientific Center of Roentgenoradiology	Moscow
Russian Federation	Clinical Diagnostic Centre of Nizhny Novgorod Region	Nizhny Novgorod
Russian Federation	Privolzhsky District Medical Centre	Nizhny Novgorod
Russian Federation	Clinical Oncology Dispensary	Omsk
Russian Federation	LLC Novaya Clinica	Pyatigorsk
Russian Federation	Private Medical Institution Euromedservice	Saint Petersburg
Russian Federation	Russian Scientific Center of Radiology and Surgical Technologies	Sankt-Peterburg
Russian Federation	Tambov Regional Oncology Clinical Dispansary	Tambov
Russian Federation	Multifunctional clinical medical center 'Medical city'	Tyumen
Spain	Hosp Clinic de Barcelona	Barcelona
Spain	Hosp. Del Mar	Barcelona
Spain	Hosp Univ Fund Jimenez Diaz	Madrid
Spain	Hosp. Clinico San Carlos	Madrid
Spain	Hosp. Univ. Hm Sanchinarro	Madrid
Spain	Hosp. Univ. Ramon Y Cajal	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 Alarcon
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 Del Rocio	Sevilla
Spain	Hosp. Virgen Macarena	Sevilla
Spain	Hosp. Clinico Univ. de Valencia	Valencia
Spain	Instituto Valenciano de Oncologia	Valencia
Taiwan	Kaohsiung Medical University Chung-Ho Memorial Hospital	Kaohsiung
Taiwan	Kaohsiung Chang Gung Memorial Hospital	Kaohsiung City
Taiwan	China Medical University Hospital	Taichung City
Taiwan	National Cheng Kung University Hospital	Tainan
Taiwan	National Taiwan University Hospital	Taipei City
Taiwan	Chang-Gung Memorial Hospital, LinKou Branch	Taoyuan
Turkey	Adana Acibadem Hospital	Adana
Turkey	Dr Abdurrahman Yurtaslan Oncology Training and Research Hospital	Ankara
Turkey	Hacettepe University Medical Faculty	Ankara
Turkey	Memorial Ankara Hastanesi	Ankara
Turkey	Adnan Menderes University Training and Research Hospital	Aydin
Turkey	Trakya University Medical Faculty	Edirne
Turkey	Istanbul Medeniyet University Goztepe Training and Research Hospital	Istanbul
Turkey	Istanbul University Cerrahpasa Medical Faculty	Istanbul
Turkey	Ege University	Izmir
Turkey	Kocaeli University Medical Faculty	Kocaeli
Turkey	Necmettin Erbakan University Meram Medical Faculty	Konya
Turkey	Karadeniz Teknik University Medical Faculty	Trabzon
United Kingdom	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 States	Rocky Mountain Cancer Centers	Aurora	Colorado
United States	Levine Cancer Institute, Carolinas HealthCare System	Charlotte	North Carolina
United States	Texas Oncology, P.A.	Fort Worth	Texas
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	Penn State Hershey Cancer Institute	Hershey	Pennsylvania
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Norton Cancer Institute	Louisville	Kentucky
United States	Weill Cornell Medical College - NY Presbyterian Hospital	New York	New York
United States	Virginia Oncology Associates	Norfolk	Virginia
United States	Maryland Oncology Hematology, PA	Rockville	Maryland
United States	Toledo Clinic Cancer Centers	Toledo	Ohio
United States	White Plains Hospital Center for Cancer Care	White Plains	New York

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Countries where clinical trial is conducted

United States,  Belarus,  Belgium,  Brazil,  France,  Italy,  Korea, Republic of,  Poland,  Russian Federation,  Spain,  Taiwan,  Turkey,  United Kingdom, 

Outcome

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