A Study of Erdafitinib in Participants With Metastatic or Locally Advanced Urothelial Cancer (NCT03473743) — Italy Trial Details

Condition(s) studied

Urothelial Carcinoma

Investigational drug(s) / intervention(s)

Erdafitinib →Cetrelimab →Cisplatin →Carboplatin →

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.

Study 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.

Eligibility

Sex

ALL

Min age

18 Years

Max age

—

Healthy volunteers

No

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

Primary outcome measure(s)

Phase 1b: Number of Participants With Dose-Limiting Toxicity (DLTs) — Up to 8 weeks
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.
Phase 2: Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 by Investigator Assessment — From Day 1 up to 36 months
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.
Phase 2: Number of Participants With Treatment-emergent Adverse Event (TEAEs) — From Day 1 up to 36 months
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.

Trial sites (127)

Facility	City	Region
Rocky Mountain Cancer Centers	Aurora	Colorado
Norton Cancer Institute	Louisville	Kentucky
Maryland Oncology Hematology, PA	Rockville	Maryland
Hackensack University Medical Center	Hackensack	New Jersey
Weill Cornell Medical College - NY Presbyterian Hospital	New York	New York
White Plains Hospital Center for Cancer Care	White Plains	New York
Levine Cancer Institute, Carolinas HealthCare System	Charlotte	North Carolina
Toledo Clinic Cancer Centers	Toledo	Ohio
Penn State Hershey Cancer Institute	Hershey	Pennsylvania
Texas Oncology, P.A.	Fort Worth	Texas
The University of Texas MD Anderson Cancer Center	Houston	Texas
Virginia Oncology Associates	Norfolk	Virginia
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

+ 87 more sites — see the full list on the official registry below.

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