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

NCT06545955 | Recruiting Phase 3 FDA Drug

• 2 other identifiers: 000434U1111-1299-0176
• Study Type: interventional
• Target: 250
• Locations: 7 countries
• Sites: 66

Brief Summary

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).

Conditions

Non-muscle Invasive Bladder Cancer With Carcinoma in Situ

Outcome Measures

Primary Outcomes (1)

• Complete response

  Complete response (CR) at any time from first treatment (defined as absence of high-grade (HG) recurrence).

  up to 6 months

Secondary Outcomes (9)

• Complete response at month 3

  3 months

• Complete response at month 6

  6 months

• Durability of complete response

  Up to 24 months

• Muscle-invasive progression of disease

  up to 36 months

• Cystectomy-free survival

  up to 36 months

Study Arms (3)

Nadofaragene firadenovec

EXPERIMENTAL

Nadofaragene firadenovec (intravesical)

Drug: Nadofaragene Firadenovec

Nadofaragene firadenovec + gemcitabine & docetaxel

EXPERIMENTAL

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

Drug: Nadofaragene Firadenovec; Drug: Gemcitabine; Drug: Docetaxel

Nadofaragene firadenovec + Pembrolizumab

EXPERIMENTAL

Nadofaragene firadenovec (intravesical), and pembrolizumab (IV infusion). This arm will be closed and patients will no longer be randomised to this arm. This modification will convert ABLE-22 into a two-arm study with 1:1 randomisation between nadofaragene alone and nadofaragene + gemcitabine/docetaxel, to now N=100 in each of the 2 remaining arms. Participants already enrolled in this arm will not be impacted.

Drug: Nadofaragene Firadenovec; Drug: Pembrolizumab

Interventions

Nadofaragene Firadenovec 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.

Also known as: ADSTILADRIN

Nadofaragene firadenovec; Nadofaragene firadenovec + Pembrolizumab; Nadofaragene firadenovec + gemcitabine & docetaxel

Gemcitabine DRUG

Intravesical Gemcitabine chemotherapy, used in combination with Docetaxel.

Nadofaragene firadenovec + gemcitabine & docetaxel

Docetaxel DRUG

Intravesical Docetaxel chemotherapy, used in combination with Gemcitabine.

Nadofaragene firadenovec + gemcitabine & docetaxel

Pembrolizumab 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.

Nadofaragene firadenovec + Pembrolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Ferring Pharmaceuticals: lead

Study Sites (66)

American Institute of Research

Los Angeles, California, 90017, United States

RECRUITING

USC Kenneth Norris Jr Cancer Hospital

Los Angeles, California, 90080, United States

RECRUITING

University of California, Irvine

Orange, California, 92868, United States

RECRUITING

Genesis Research, LLC - San Diego

San Diego, California, 92123, United States

RECRUITING

Advent Health

Denver, Colorado, 80210, United States

RECRUITING

Colorado Urology - St. Anthony Hospital Campus

Lakewood, Colorado, 80228, United States

RECRUITING

Yale School of Medicine

New Haven, Connecticut, 06519, United States

RECRUITING

Medstar Georgetown University Hospital

Washington D.C., District of Columbia, 20007, United States

RECRUITING

Sarasota Memorial Healthcare System

Sarasota, Florida, 34239, United States

RECRUITING

Emory University

Atlanta, Georgia, 30322, United States

RECRUITING

Georgia Urology

Atlanta, Georgia, 30328, United States

RECRUITING

Boise VA Medical Center

Boise, Idaho, 83702, United States

RECRUITING

NextStage Clinical Research

Lisle, Illinois, 60532, United States

RECRUITING

Indiana University

Indianapolis, Indiana, 46202, United States

RECRUITING

Wichita Urology Group

Wichita, Kansas, 67226, United States

RECRUITING

Anne Arundel Urology, PA

Annapolis, Maryland, 21401, United States

RECRUITING

Chesapeake Urology Research Associates

Hanover, Maryland, 21076, United States

RECRUITING

Atlantic Health

Morristown, New Jersey, 07960, United States

RECRUITING

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

RECRUITING

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

Cheektowaga, New York, 14225, United States

RECRUITING

Northwell Health -The Arthur Smith Institute for Urology

Lake Success, New York, 11042, United States

RECRUITING

James J. Peters VA Medical Center

The Bronx, New York, 10468, United States

RECRUITING

University of Cincinnati

Cincinnati, Ohio, 45267, United States

RECRUITING

MidLantic Urology

Bala-Cynwyd, Pennsylvania, 19004, United States

RECRUITING

Keystone Urology Specialists

Lancaster, Pennsylvania, 17601, United States

RECRUITING

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

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

Carolina Urologic Research Center

Myrtle Beach, South Carolina, 29572, United States

RECRUITING

Urology Associates, P.C.

Nashville, Tennessee, 37209, United States

RECRUITING

Urology Austin

Austin, Texas, 78759, United States

RECRUITING

Urology Clinics of North Texas PLLC (Dallas)

Dallas, Texas, 75231, United States

RECRUITING

University of Texas Southwestern Medical Center - Urology Clinic

Dallas, Texas, 75390, United States

RECRUITING

Houston Methodist Hospital (Houston)

Houston, Texas, 77030, United States

RECRUITING

Virginia Mason Medical Center

Seattle, Washington, 98101, United States

RECRUITING

Prostate Cancer Centre

Calgary, Alberta, T2V 1P9, Canada

RECRUITING

Centre Hospitalier de L'Universite de Montreal

Montreal, Quebec, H2X 0A9, Canada

RECRUITING

Krajska Nemocnice Liberec

Liberec, Liberec Region, 46300, Czechia

RECRUITING

Fakultní Thomayerova Nemocnice

Prague, Prague, 14059, Czechia

RECRUITING

Fakultni nemocnice v Motole

Prague, Prague, 15006, Czechia

RECRUITING

Androgeos, spol. s r.o.

Prague, Prague, 16000, Czechia

RECRUITING

Kromerizska Nemocnice A S

Kroměříž, Zlín, 76701, Czechia

RECRUITING

CHU Clermont Ferrand - Hopital Gabriel Montpied

Clermont-Ferrand, Auvergne-Rhône-Alpes, 63000, France

RECRUITING

Hospices Civils de Lyon - Edouard Herriot Hosp.

Lyon, Auvergne-Rhône-Alpes, 69003, France

RECRUITING

CHU Toulouse - Hopital Rangueil

Toulouse, Huate-Garonne, 31059, France

RECRUITING

CHU Nantes - Hotel Dieu

Nantes, Nantes, 44093, France

RECRUITING

CHU de Bordeaux - Hôpital Pellegrin

Bordeaux, New Aquitaine, 33076, France

RECRUITING

Centre Hospitalier Universitaire De Nimes (Nîmes)

Nîmes, Occitanie, 30900, France

RECRUITING

Centre Hospitaliser Universitaire de Lyon Sud

Lyon, Rhone.Alpe, 69310, France

RECRUITING

Hopital La Pitie Salpetriere

Paris, 75013, France

RECRUITING

APHP - Hopital Bichat

Paris, Île-de-France Region, 75018, France

RECRUITING

IN-VIVO Bydgoszcz

Bydgoszcz, Kuyavian-Pomeranian Voivodeship, 85-048, Poland

RECRUITING

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

Poznan, Wielkopolska, 61731, Poland

RECRUITING

Medical Concierge Centrum Medyczne

Warsaw, Woj. Mazowieckie, 02798, Poland

RECRUITING

Korea University Anam Hospital

Seoul, Seoul, 02841, South Korea

RECRUITING

Samsung Medical Center

Seoul, Seoul, 06351, South Korea

RECRUITING

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

Santander, Cantabria, 39008, Spain

RECRUITING

Hospital del Mar

Barcelona, Catalonia, 08003, Spain

RECRUITING

Hospital Clinic De Barcelona - University of Barcelona

Barcelona, Catalonia, 08036, Spain

RECRUITING

Hospital Universitario Reina Sofia

Córdoba, Cordoba, 14004, Spain

RECRUITING

Hospital Universitario de A Coruna

A Coruña, Galicia, 15006, Spain

RECRUITING

Hospital Universitario Fundacion Alcorcon

Alcorcón, Madrid, 28922, Spain

RECRUITING

Clinica Universidad de Navarra - Madrid

Madrid, Madrid, 28027, Spain

RECRUITING

Hospital Universitario 12 De Octubre (Madrid)

Madrid, Madrid, 28041, Spain

RECRUITING

Universidad Autonoma de Madrid. Hospital Universitario La Paz

Madrid, Madrid, 28046, Spain

RECRUITING

Clinica Universidad de Navarra - Pamplona

Pamplona, Navarre, 31008, Spain

RECRUITING

Hospital Universitario Basurto

Bilbao, Vizcaya, Spain

RECRUITING

Servicio Andaluz de Salud (SAS) - Hospital Universitario Virgen de la Victoria (HUVV)

Málaga, 29010, Spain

RECRUITING

MeSH Terms

Interventions

Gemcitabine; Docetaxel; pembrolizumab

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• Global Clinical Compliance

  Ferring Pharmaceuticals

  STUDY DIRECTOR

Central Study Contacts

Ferring Pharmaceuticals

CONTACT

833-548-1402 (US/Canada); disclosure@ferring.com

Ferring Pharmaceuticals

CONTACT

+1862-286-5200 (not US/Canada); disclosure@ferring.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 6, 2024
• First Posted: August 9, 2024
• Study Start: October 1, 2024
• Primary Completion (Estimated): June 30, 2028
• Study Completion (Estimated): December 31, 2030
• Last Updated: April 20, 2026

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

CZ (5); PL (3); FR (9); CA (2); US (33); KR (2); ES (12)