Clinical trial NCT06511648: Erdafitinib Monotherapy or in Combination With Cetrelimab in Muscle-invasive Bladder Cancer Patients With Fibroblast Growth Factor Receptor (FGFR ) Gene Alterations
Official title: 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 Fibroblast Growth Factor Receptor ( FGFR ) Gene Alterations
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Muscle-invasive Bladder Cancer
Keywords: Urothelial carcinoma
Lead sponsor: Spanish Oncology Genito-Urinary Group
Sponsor class: OTHER
Collaborators: name: Janssen-Cilag Ltd.
name: Pivotal S.L.
First posted: 2024-07-22
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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 Fibroblast Growth Factor Receptor (FGFR )gene alterations and are ineligible for or refuse cisplatin based neoadjuvant chemotherapy.

Detailed description: The aim of the study is to assess the antitumor activity measured as ypT0 rate, defined as no evidence of residual disease based on pathological review of the surgical specimen (pCR) and tumour downstaging (\<ypT2). Patients must have a MIBC (cT2-T4a N0/N1 M0) who harbour selected FGFR alterations stated in the protocol and are either ineligible for or refuse cisplatin-based neoadjuvant chemotherapy, as defined by consensus criteria (see 6.1 Inclusion criteria).

Once it is confirmed that the subjects fulfil the eligibility criteria and have signed the informed consent form, they will receive erdafitinib alone (cohort 1) or erdafitinib in combination with cetrelimab (cohort 2).

Patients will receive neoadjuvant treatment with erdafitinib alone (cohort 1) or erdafitinib plus cetrelimab (cohort 2) before proceeding to Radical Cystectomy (RC) (to be performed within 2 - 6 weeks after the last study drug treatment)

Cohort 1: patients will receive erdafitinib Cohort 2: patients will receive erdafitinib in combination with cetrelimab intravenously (IV)

Radiological assessment: A Computed Tomography /Magnetic Resonance Imaging and/or Positron Emission Tomography (per standard local imaging practices) will be scheduled as follow:

* Basal assessment: during screening period (no more than 28 days before Cycle1, Day 1(C1D1)
* Response assessment: At the end of treatment period allowing time for imaging review in advance of Radical cystectomy (RC).
* Follow-up assessment: an image evaluation must be done at first follow-up visit and thereafter, it will be schedule according to local standards and as clinically indicated.

A local pathological assessment will be done on specimens obtained during RC (for co-primary endpoints). Thereafter, during the follow-up period, pathological assessments will be scheduled according to local standards and as clinically indicated.

Patients with disease progression during the treatment phase will be discontinued from the study and will receive their treatment according to the investigator's judgment and monitored to evaluate Overal Survival .

Eligibility criteria: 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 Transurethral Resection of Bladder Tumor (TURBT) performed no later than 3 months prior to start the screening visit.
3. Pure or predominant (≥50%) urotelial Cancer (UC) histology as determined at the local site.
4. Age ≥ 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

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.
4. Prior FGFR-targeted or an immune checkpoint inhibitor (antiPD1/PDL1 )systemic therapy.
5. Prior systemic therapy, radiation therapy, or surgery for bladder cancer

Primary outcomes:
measure: Pathological complete response (pCR)
timeFrame: After a maximum of 30 weeks from the start of treatment (First Followup visit ) on specimens obtained during radical cystectomy.
measure: Pathological downstaging response <ypT2
timeFrame: After a maximum of 30 weeks from the start of treatment (First Followup visit ) on specimens obtained during radical cystectomy.
Secondary outcomes:
measure: Rate of pathological downstaging (pDS)
timeFrame: During treatment (27 months)
measure: Event-free Survival rate.
timeFrame: During follow-up period (36 months)
measure: Overall Survival
timeFrame: During follow-up period (36 months)
measure: Overall Response Rate
timeFrame: During treatment (27 months)
measure: Adverse events.
timeFrame: During treatment (27 months) and follow-up period (36 months)
measure: Rate of delay of surgery
timeFrame: During treatment (27 months) and follow-up period (36 months)
Other outcomes:
Locations:
city: Clermont-Ferrand
country: France
facility: CLCC Jean Perrin
city: Lyon
country: France
facility: CLCC Léon Bérard
city: Paris
country: France
facility: Institut Mutualiste Montsouris
city: Toulouse
country: France
facility: IUCT
city: Villejuif
country: France
facility: Institut Gustave Roussy
city: Milan
country: Italy
facility: IRCCS San Raffaele Hospital and Scientific Institute
city: Turin
country: Italy
facility: Ospedale Molinette
city: Turi
country: Italy
facility: A.O. Ordine Mauriziano, Ospedale Umberto I
city: Barcelona
country: Spain
facility: Hospital Clínic De Barcelona
state: Cataluña
city: Barcelona
country: Spain
facility: Hospital De Sabadell (Parc Taulí)
state: Cataluña
city: Coruña
country: Spain
facility: Complexo Hospitalario Universitario A Coruña
state: Galicia
city: Lugo
country: Spain
facility: Hospital Universitario Lucus Augusti
state: Galicia
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Valencia
country: Spain
facility: Fundación Instituto Valenciano De Oncología
city: Lancaster
country: United Kingdom
facility: University Hospitals of Morecambe Bay NHS Foundation Trust
city: London
country: United Kingdom
facility: The Royal Marsden NHS Foundation Trust
city: London
country: United Kingdom
facility: Barts Health NHS Trust
city: London
country: United Kingdom
facility: Charing Cross Hospital
city: Sheffield
country: United Kingdom
facility: Sheffield Teaching Hospitals NHS Foundation Trust
Study officials:
References: