Clinical Trials Register

Summary
EudraCT Number:	2022-002586-15
Sponsor's Protocol Code Number:	SOGUG-2020-IEC(VEJ)-11
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2023-01-04
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Italy - Italian Medicines Agency

A.2

EudraCT number

2022-002586-15

A.3

Full title of the trial

A Phase 2, open-label, multi-centre, multi-national interventional trial to evaluate the efficacy and safety of erdafitinib (ERDA) monotherapy and erdafitinib (ERDA) and cetrelimab (CET) combination as neoadjuvant treatment in cisplatin-ineligible patients with muscle-invasive bladder cancer (MIBC) whose tumours express FGFR gene alterations.

Studio interventistico di fase II, in aperto, multicentrico e multinazionale volto a valutare l'efficacia e la sicurezza di erdafitinib (ERDA) in monoterapia e della combinazione di erdafitinib (ERDA) e cetrelimab (CET) come trattamento neoadiuvante in pazienti affetti da carcinoma della vescica muscolo-invasivo (MIBC) non idonei al trattamento con cisplatino i cui tumori esprimono alterazioni del gene FGFR.

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Erdafitinib (ERDA) alone or in combination with cetrelimab (CET) as neoadjuvant treatment (prior to surgery) in subjects with muscle-invasive bladder cancer (MIBC) whose tumours express FGFR gene alterations and are ineligible for receiving cisplatin treatment

Erdafitinib (ERDA) da solo o in combinazione con cetrelimab (CET) come trattamento neoadiuvante (prima dell'intervento chirurgico) in soggetti con carcinoma della vescica muscolo-invasivo (MIBC) i cui tumori esprimono alterazioni del gene FGFR e non sono eleggibili al trattamento con cisplatino

A.3.2

Name or abbreviated title of the trial where available

SOGUG-NEOWIN TRIAL

ENSAYO SOGUG-NEOWIN

A.4.1

Sponsor's protocol code number

SOGUG-2020-IEC(VEJ)-11

A.5.4

Other Identifiers

Name:

N/A

Number:

N/A

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Spanish Oncology Genitourinary Group (SOGUG)
B.1.3.4	Country	Spain
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Janssen Pharmaceutica NV
B.4.2	Country	Belgium
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Spanish Oncology Genito Urinary Group (SOGUG)
B.5.2	Functional name of contact point	Isabel Grau Miró
B.5.3	Address:
B.5.3.1	Street Address	Velázquez 7
B.5.3.2	Town/ city	Madrid
B.5.3.3	Post code	28001
B.5.3.4	Country	Spain
B.5.4	Telephone number	610286915
B.5.6	E-mail	trialmanager@sogug.es

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Cetrelimab
D.3.2	Product code	[JNJ-63723283]
D.3.4	Pharmaceutical form
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.1	CAS number	2050478-92-5
D.3.9.2	Current sponsor code	JNJ-63723283
D.3.9.4	EV Substance Code	SUB193853
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	30
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	Yes
D.3.11.13.1	Other medicinal product type	It is a fully human immunoglobulin G4(IgG4) kappa monoclonal antibody (mAb)
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Balversa
D.2.1.1.2	Name of the Marketing Authorisation holder	Janssen Biotech Inc.
D.2.1.2	Country which granted the Marketing Authorisation	United States
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Erdafitinib
D.3.2	Product code	[JNJ-42756493]
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Erdafitinib
D.3.9.1	CAS number	1346242-81-6
D.3.9.2	Current sponsor code	JNJ-42756493
D.3.9.4	EV Substance Code	SUB192453
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	up to
D.3.10.3	Concentration number	8
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Muscle-invasive bladder cancer (MIBC)

Tumore della vescica muscolo-invasivo (MIBC)

E.1.1.1

Medical condition in easily understood language

Bladder cancer that spreads beyond the inner lining of the bladder and into the muscle layer

Tumore della vescica che si diffonde oltre il rivestimento interno della vescica fino allo strato muscolare

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

•To assess the antitumor activity measured as pT0N0 rate, defined as no evidence of residual disease based on pathological review of the surgical specimen
•To assess the percentage of pathological downstaging response

• Valutare l'attività antitumorale misurata come tasso di pT0N0, definito come nessuna evidenza di malattia residua sulla base della revisione patologica del campione chirurgico.
• Valutare la percentuale di risposta in termini di downstaging patologico

E.2.2

Secondary objectives of the trial

•To evaluate the percentage of tumour downstaging
•To estimate the event-free survival (EFS)
•To estimate the overall survival (OS).
•To evaluate the Objective Response Rate (ORR) after neoadjuvant treatment
•To assess the safety profile and tolerability of both schemes
•To calculate the rate of delay of surgery.

• Valutare la percentuale di downstaging del tumore, definito come stadio della stadiazione TNM patologica inferiore a quello della stadiazione TNM clinica.
• Stimare il tasso di sopravvivenza libera da eventi (Event-Free Survival, EFS), definito come progressione della malattia, decesso o qualsiasi evento che impedisca l'esecuzione della RC, compreso l'avvio di qualsiasi terapia aggiuntiva prima della RC.
• Stimare la sopravvivenza complessiva (Overall Survival, OS).
• Valutare il tasso di risposta obiettiva (Objective Response Rate, ORR) secondo i criteri RECIST v1.1 nei soggetti dopo il trattamento neoadiuvante (prima della RC).
• Valutare il profilo di sicurezza e la tollerabilità sia di erdafitinib in monoterapia sia di erdafitinib in combinazione con cetrelimab.
• Calcolare il tasso di ritardo nell'intervento chirurgico.

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

Other types of substudies
Specify title, date and version of each substudy with relative objectives: Biomarkers Analysis

Altre tipologie di sottostudi
specificare il titolo, la data e la versione di ogni sottostudio con i relativi obiettivi: Analisi dei biomarcatori

E.3

Principal inclusion criteria

1)Written informed consent stating that he or she understands the purpose of the study and the procedures involved and agrees to participate in the study.
2)Histologically confirmed diagnosis of MIBC (Stage T2-4a N0/N1 M0) obtained via a diagnostic or maximal TURBT performed no later than 3 months prior to start the screening visit.
3)Pure or predominant (major equal to 50%) UC histology as determined at the local site.
4)Age major equal to 18 years.
5)Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
6)Decline or ineligible (“unfit”) for cisplatin-based chemotherapy
7)Presence of a selected FGFR alteration on analysis of tumour biopsy
8)Adequate organ function
9)No other malignancy
10)Willingness to avoid pregnancy or fathering children

1) Consenso informato scritto in cui si afferma che il paziente comprende lo scopo dello studio e le procedure coinvolte e accetta di partecipare allo studio.
2) Diagnosi di MIBC confermata istologicamente (stadio T2-4a N0/N1 M0) ottenuta mediante resezione transuretrale di cancro della vescica (Transurethral Resection Bladder Tumor, TURBT) diagnostica o massima eseguita entro e non oltre 3 mesi prima dell'inizio della visita di screening.
3) Istologia di carcinoma uroteliale (Urothelial Carcinoma, UC) pura o predominante (maggiore uguale 50%) determinata presso il centro locale.
4) Età maggiore uguale 18 anni.
5) Stato di performance secondo l'Eastern Cooperative Oncology Group (ECOG) pari a 0-1.
6) Rifiuto o mancata idoneità per la chemioterapia a base di cisplatino
7) Presenza di un'alterazione di FGFR selezionata all'analisi della biopsia tumorale, che mostri una delle nove aberrazioni basate sul pannello Therascreen FGFR di Qiagen (Tabella 1). Possono essere accettati referti locali basati su test convalidati (con successiva conferma mediante il Therascreen di Qiagen). I pazienti con test locale positivo non dovranno attendere la conferma per essere arruolati. Tutti i pazienti dovranno fornire un campione di tumore per il test Therascreen di Qiagen. In caso di discrepanze, prevarrà la determinazione locale.
8) Adeguata funzione d'organo entro i 14 giorni precedenti il trattamento e prima del Giorno 1 del Ciclo 1 (è consentita la gestione medica)
9) Nessun'altra neoplasia maligna (diagnosi negli ultimi 3 anni), ad eccezione del carcinoma cutaneo non melanoma trattato (basocellulare o squamocellulare), del carcinoma in situ della cervice e del carcinoma prostatico a basso rischio.
10) Disponibilità ad evitare l'avvio di una gravidanza o la procreazione

E.4

Principal exclusion criteria

1)Clinical evidence of N2-N3 tumours or metastatic bladder cancer.
2)Has tumour with any neuroendocrine or small cell component.
3)Patients who are not considered fit for cystectomy or reject cystectomy.
5)Prior FGFR-targeted or antiPD1/PDL1 systemic therapy.
6)Prior systemic therapy, radiation therapy, or surgery for bladder cancer

1) Evidenze cliniche di tumori N2-N3 o cancro della vescica metastatico.
2) Tumore con qualsiasi componente neuroendocrina o a piccole cellule.
3) Pazienti non considerati idonei per la cistectomia o che rifiutano la cistectomia.
4) Pazienti con comorbilità che precluderanno loro l'intervento sperimentale.
5) Terapia sistemica precedente anti-PD1/PDL1 o mirata a FGFR.
6) Non sono consentite precedenti terapie sistemiche, radioterapia o interventi chirurgici per il cancro della vescica diversi dalla TURBT o dalle biopsie. Il trattamento precedente con BCG o altro trattamento endovescicale del carcinoma della vescica non muscolo-invasivo (non-MIBC) è consentito se completato almeno 6 settimane prima dell'inizio del trattamento in studio.

E.5 End points

E.5.1

Primary end point(s)

Primary endpoint(s)
•Pathological complete response (pCR).
•Pathological downstaging <ypT2.

Endpoint primario
-Risposta patologica completa (pCR).
-Downstaging patologico <ypT2.

E.5.1.1

Timepoint(s) of evaluation of this end point

After a maximum of 30 weeks from the start of treatment (First Follow- up visit ) on specimens obtained during radical cystectomy.

Dopo un massimo di 30 settimane dall'inizio del trattamento (prima visita di follow-up) su campioni ottenuti durante la cistectomia radicale.

E.5.2

Secondary end point(s)

Secondary endpoints
•Rate of pathological downstaging (pDS)
•Event-free Survival rate.
•OS.
•ORR according to RECIST, after neoadjuvant treatment.
•Adverse events.
•Rate of delay of surgery (classed as a delay event if performed > 6 weeks after last dose of treatment).

Endpoint secondari
-Tasso di downstaging patologico (pDS)
-Tasso di sopravvivenza libera da eventi.
-OS.
-ORR secondo RECIST, dopo trattamento neoadiuvante.
-Eventi avversi.
-Tasso di ritardo dell'intervento chirurgico (classificato come evento di ritardo se eseguito > 6 settimane dopo l'ultima dose di trattamento)

E.5.2.1

Timepoint(s) of evaluation of this end point

During treatment and follow-up period.

Durante il trattamento e il periodo di follow-up.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

aperto

open

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

Information not present in EudraCT

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

France

Spain

Italy

United Kingdom

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

Ultima visita dell'ultimo soggetto reclutato

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

Yes

F.3.3.2

Women of child-bearing potential using contraception

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

None

Nessuno

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2023-03-31

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2023-07-26

P. End of Trial
P.	End of Trial Status	Ongoing

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