A Trial to Evaluate Intravesical Nadofaragene Firadenovec Alone or in Combination With Chemotherapy or Immunotherapy in Participants With High-grade BCG Unresponsive Non-muscle Invasive Bladder Cancer

NCT ID: NCT06545955

Last Updated: 2025-11-13

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

250 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-10-01

Study Completion Date

2030-12-31

Brief Summary

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The pivotal phase 3 trial (rAd-IFN-CS 003) evaluating the efficacy of nadofaragene firadenovec showed that 55 (53.4%) of 103 subjects with CIS ± high-grade Ta/T1 achieved a complete response (CR) at 3 months. In this trial, the safety and efficacy of intravesical instillation of nadofaragene firadenovec alone or in combination with chemotherapy or immunotherapy will be evaluated in participants with NMIBC CIS (± high-grade Ta/T1).

Detailed Description

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Conditions

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Non-muscle Invasive Bladder Cancer With Carcinoma in Situ

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Nadofaragene firadenovec

Nadofaragene firadenovec (intravesical)

Group Type EXPERIMENTAL

Nadofaragene Firadenovec

Intervention Type DRUG

vector-based gene therapy for NMIBC treatment to potentiate durable therapeutic responses by interferon (IFN) alfa-2b (IFN-α2b) amplification. It is a non-replicating recombinant adenovirus serotype 5 vector containing a transgene encoding the human IFN-α2b gene.

Nadofaragene firadenovec + gemcitabine & docetaxel

Nadofaragene firadenovec (intravesical), and sequential gemcitabine and docetaxel (intravesical)

Group Type EXPERIMENTAL

Nadofaragene Firadenovec

Intervention Type DRUG

vector-based gene therapy for NMIBC treatment to potentiate durable therapeutic responses by interferon (IFN) alfa-2b (IFN-α2b) amplification. It is a non-replicating recombinant adenovirus serotype 5 vector containing a transgene encoding the human IFN-α2b gene.

Gemcitabine

Intervention Type DRUG

Intravesical Gemcitabine chemotherapy, used in combination with Docetaxel.

Docetaxel

Intervention Type DRUG

Intravesical Docetaxel chemotherapy, used in combination with Gemcitabine.

Nadofaragene firadenovec + pembrolizumab

Nadofaragene firadenovec (intravesical), and pembrolizumab (IV infusion)

Group Type EXPERIMENTAL

Nadofaragene Firadenovec

Intervention Type DRUG

vector-based gene therapy for NMIBC treatment to potentiate durable therapeutic responses by interferon (IFN) alfa-2b (IFN-α2b) amplification. It is a non-replicating recombinant adenovirus serotype 5 vector containing a transgene encoding the human IFN-α2b gene.

Pembrolizumab

Intervention Type DRUG

Pembrolizumab is an FDA approved immune checkpoint inhibitor which restores the anti-tumour immune response by blocking the programmed cell death protein 1 (PD-1). Pembrolizumab is administered via intravenous (IV) infusion.

Interventions

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Nadofaragene Firadenovec

vector-based gene therapy for NMIBC treatment to potentiate durable therapeutic responses by interferon (IFN) alfa-2b (IFN-α2b) amplification. It is a non-replicating recombinant adenovirus serotype 5 vector containing a transgene encoding the human IFN-α2b gene.

Intervention Type DRUG

Gemcitabine

Intravesical Gemcitabine chemotherapy, used in combination with Docetaxel.

Intervention Type DRUG

Docetaxel

Intravesical Docetaxel chemotherapy, used in combination with Gemcitabine.

Intervention Type DRUG

Pembrolizumab

Pembrolizumab is an FDA approved immune checkpoint inhibitor which restores the anti-tumour immune response by blocking the programmed cell death protein 1 (PD-1). Pembrolizumab is administered via intravenous (IV) infusion.

Intervention Type DRUG

Other Intervention Names

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ADSTILADRIN

Eligibility Criteria

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Inclusion Criteria

* Diagnosed, as documented, with carcinoma in situ (CIS) ±Ta/T1 high-grade disease.

* For T1 disease biopsies should contain muscle fibres.
* Unresponsive to ≥2 courses of Bacillus Calmette-Guerin (BCG) therapy within the last 12 months. BCG-unresponsive refers to participants with high-grade non-muscle invasive bladder cancer (NMIBC) who are unlikely to benefit from and who will not be receiving further intravesical BCG. The term "BCG-Unresponsive" includes participants who did not respond to BCG treatment and have a persistent high-grade recurrence within 12 months after BCG was initiated, and those who despite an initial complete response to BCG, relapse with CIS within 12 months of their last intravesical treatment with BCG or relapse with high-grade Ta/T1 NMIBC within 6 months of their last intravesical treatment with BCG. The following criteria define the participants who may be included in the trial:

* Have received at least 2 courses of BCG within a 12 month period - defined as at least 5 of 6 induction BCG instillations and at least 2 of 3 instillations of maintenance BCG, or at least 2 of 6 instillations of a second induction course, where maintenance BCG is not given.

o Exception: those who have T1 high-grade disease at 1st evaluation after induction BCG alone (at least 5 of 6 doses) may qualify in the absence of disease progression
* At the time of tumour recurrence, participants with CIS alone or high-grade Ta/T1 with CIS should be within 12 months of last exposure to BCG
* No maximum limit to the amount of BCG administered
* All visible papillary tumours must be resected and those with persistent T1 disease on transurethral resection of bladder tumour (TURBT) should undergo an additional re-TURBT within 14 to 70 days prior to beginning trial treatment. Obvious areas of CIS should also be fulgurated
* Eastern Cooperative Oncology Group (ECOG) status ≤2
* Aged ≥18 years at the time of consent
* Available for the whole duration of the trial
* Life expectancy \>2 years, in the opinion of the investigator
* Absence of concomitant upper tract urothelial carcinoma or urothelial carcinoma within the prostatic urethra. Freedom from upper tract disease (if clinically indicated) as indicated by no evidence of upper tract tumour by either intravenous pyelogram, retrograde pyelogram, computed tomography (CT) scan with or without urogram, or magnetic resonance imaging (MRI) with or without urogram performed within 6 months of enrolment. Absence of locally advanced disease as assessed by CT scan or MRI
* Participants who elect not to undergo cystectomy
* Participants with prostate cancer on active surveillance at low risk for progression are permitted to be included into the trial at the discretion of the investigator
* Females of reproductive potential must have a negative highly sensitive urine or serum pregnancy test upon entry into this trial and be willing to use highly effective contraception during treatment with the investigational medicinal product and for 6 months following the last dose. Otherwise, female participants must be post-menopausal (no menstrual period for a minimum of 12 months, as confirmed by follicle-stimulating hormone levels) or surgically sterile
* Male subjects must use highly effective contraception and a condom during sexual contact regardless of partner's childbearing potential, until 3 months following the last trial drug administration.

Exclusion Criteria

* Current or previous evidence of muscle-invasive (muscularis propria) or metastatic disease presented at the screening visit. Examples of increased risk of muscle-invasive disease include but are not limited to:

* Presence of lymphovascular invasion and / or micropapillary, sarcomatoid, plasmacytoid and / or neuroendocrine disease as shown in the histology of the biopsy sample
* Participants with CIS+T1 disease accompanied by the presence of hydronephrosis secondary to the primary tumour
* Current systemic therapy for bladder cancer other than investigational medicinal products used in randomisation arm
* Current or prior investigational treatment for BCG-unresponsive NMIBC or any other investigational drug (drug used in a clinical trial, i.e drug used in a Ferring sponsored non interventional study does not apply) within 1 month prior to screening
* Current or prior pelvic external beam radiotherapy within 2 years of screening
* Prior treatment with nadofaragene firadenovec at any time
* Prior systemic therapy for bladder cancer at any time
* Prior intravesical chemotherapy for the treatment of BCG-unresponsive NMIBC
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Ferring Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Global Clinical Compliance

Role: STUDY_DIRECTOR

Ferring Pharmaceuticals

Locations

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American Institute of Research

Los Angeles, California, United States

Site Status RECRUITING

USC Kenneth Norris Jr Cancer Hospital

Los Angeles, California, United States

Site Status RECRUITING

University of California, Irvine

Orange, California, United States

Site Status RECRUITING

Genesis Research, LLC - San Diego

San Diego, California, United States

Site Status RECRUITING

Advent Health

Denver, Colorado, United States

Site Status RECRUITING

Yale School of Medicine

New Haven, Connecticut, United States

Site Status RECRUITING

Sarasota Memorial Healthcare System

Sarasota, Florida, United States

Site Status RECRUITING

Emory University

Atlanta, Georgia, United States

Site Status RECRUITING

Georgia Urology

Atlanta, Georgia, United States

Site Status RECRUITING

Boise VA Medical Center

Boise, Idaho, United States

Site Status RECRUITING

Indiana University

Indianapolis, Indiana, United States

Site Status RECRUITING

Wichita Urology Group

Wichita, Kansas, United States

Site Status RECRUITING

Chesapeake Urology Research Associates

Hanover, Maryland, United States

Site Status RECRUITING

Michigan Institute of Urology

Troy, Michigan, United States

Site Status RECRUITING

Atlantic Health

Morristown, New Jersey, United States

Site Status RECRUITING

Roswell Park Cancer Institute

Buffalo, New York, United States

Site Status RECRUITING

Great Lakes Physician PC d/b/a Western new York Urology Associates

Cheektowaga, New York, United States

Site Status RECRUITING

Northwell Health -The Arthur Smith Institute for Urology

Lake Success, New York, United States

Site Status RECRUITING

Premier Medical Group of the Hudson Valley

Poughkeepsie, New York, United States

Site Status RECRUITING

James J. Peters VA Medical Center

The Bronx, New York, United States

Site Status RECRUITING

University of Cincinnati

Cincinnati, Ohio, United States

Site Status RECRUITING

MidLantic Urology

Bala-Cynwyd, Pennsylvania, United States

Site Status RECRUITING

Keystone Urology Specialists

Lancaster, Pennsylvania, United States

Site Status RECRUITING

University of Pennsylvania - Perelman Center for Advanced Medicine - Penn Urology

Philadelphia, Pennsylvania, United States

Site Status RECRUITING

Carolina Urologic Research Center

Myrtle Beach, South Carolina, United States

Site Status RECRUITING

Houston Methodist Hospital (Houston)

Houston, Texas, United States

Site Status RECRUITING

Fakultní Thomayerova Nemocnice

Prague, Prague, Czechia

Site Status RECRUITING

Clinical Research Center Spółka z ograniczoną odpowiedzialnością Medic-R Sp.k.

Poznan, Wielkopolska, Poland

Site Status RECRUITING

Medical Concierge Centrum Medyczne

Warsaw, Woj. Mazowieckie, Poland

Site Status RECRUITING

Instituto de Investigacion Valdecilla (IDIVAL) / Hospital universitario Marques de Valdecilla

Santander, Cantabria, Spain

Site Status RECRUITING

Hospital Universitario Reina Sofia

Córdoba, Cordoba, Spain

Site Status RECRUITING

Hospital Universitario de A Coruna

A Coruña, Galicia, Spain

Site Status RECRUITING

Clinica Universidad de Navarra - Madrid

Madrid, Madrid, Spain

Site Status RECRUITING

Hospital Universitario 12 De Octubre (Madrid)

Madrid, Madrid, Spain

Site Status RECRUITING

Clinica Universidad de Navarra - Pamplona

Pamplona, Navarre, Spain

Site Status RECRUITING

Countries

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United States Czechia Poland Spain

Central Contacts

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Ferring Pharmaceuticals

Role: CONTACT

Phone: 833-548-1402 (US/Canada)

Email: [email protected]

Ferring Pharmaceuticals

Role: CONTACT

Phone: +1862-286-5200 (not US/Canada)

Email: [email protected]

Facility Contacts

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Role: primary

Other Identifiers

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U1111-1299-0176

Identifier Type: OTHER

Identifier Source: secondary_id

000434

Identifier Type: -

Identifier Source: org_study_id