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 (ABLE-22)

A Phase 3, Randomised, Multi-center, Open Label Trial to Evaluate the Safety and Efficacy of Intravesical Nadofaragene Firadenovec Alone or in Combination With Chemotherapy or Immunotherapy in Participants With High-grade Bacillus Calmette-Guerin Therapy (BCG) Unresponsive Non-muscle Invasive Bladder Cancer (NMIBC)

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).

Study Overview

• Status: Recruiting
• Conditions: Non-muscle Invasive Bladder Cancer With Carcinoma in Situ
• Intervention / Treatment: Drug: Nadofaragene Firadenovec; Drug: Gemcitabine; Drug: Docetaxel; Drug: Pembrolizumab

• Study Type: Interventional
• Enrollment (Estimated): 250
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Ferring Pharmaceuticals; Phone Number: 833-548-1402 (US/Canada); Email: disclosure@ferring.com
• Study Contact Backup: Name: Ferring Pharmaceuticals; Phone Number: +1862-286-5200 (not US/Canada); Email: disclosure@ferring.com

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2V 1P9
      • Recruiting
      • Prostate Cancer Centre
  • Ontario
    • Toronto, Ontario, Canada, M5G 1Z5
      • Recruiting
      • University Health Network UHN - Princess Margaret Cancer Centre
  • Quebec
    • Montreal, Quebec, Canada, H2X 0A9
      • Recruiting
      • Centre Hospitalier de l'Universite de Montreal
• Czechia
  • Liberec Region
    • Liberec, Liberec Region, Czechia, 46300
      • Recruiting
      • Krajská nemocnice Liberec
  • Prague
    • Prague, Prague, Czechia, 14059
      • Recruiting
      • Fakultni Thomayerova nemocnice
    • Prague, Prague, Czechia, 15006
      • Recruiting
      • Fakultni nemocnice v Motole
    • Prague, Prague, Czechia, 16000
      • Recruiting
      • Androgeos, spol. s r.o.
  • Zlín
    • Kroměříž, Zlín, Czechia, 76701
      • Recruiting
      • Kromerizska Nemocnice A S
• France
  • Paris, France, 75013
    • Recruiting
    • Hôpital La Pitié Salpêtrière
  • Auvergne-Rhône-Alpes
    • Clermont-Ferrand, Auvergne-Rhône-Alpes, France, 63000
      • Recruiting
      • CHU Clermont Ferrand - Hopital Gabriel Montpied
    • Lyon, Auvergne-Rhône-Alpes, France, 69003
      • Recruiting
      • Hospices Civils de Lyon - Edouard Herriot Hosp.
  • Huate-Garonne
    • Toulouse, Huate-Garonne, France, 31059
      • Recruiting
      • CHU Toulouse - Hôpital Rangueil
  • Nantes
    • Nantes, Nantes, France, 44093
      • Recruiting
      • CHU Nantes - Hotel Dieu
  • New Aquitaine
    • Bordeaux, New Aquitaine, France, 33076
      • Recruiting
      • CHU de Bordeaux - Hôpital Pellegrin
  • Occitanie
    • Nîmes, Occitanie, France, 30900
      • Recruiting
      • Centre Hospitalier Universitaire De Nimes (Nîmes)
  • Rhone.Alpe
    • Lyon, Rhone.Alpe, France, 69310
      • Recruiting
      • Centre Hospitaliser Universitaire de Lyon Sud
  • Île-de-France Region
    • Paris, Île-de-France Region, France, 75018
      • Recruiting
      • APHP - Hopital Bichat
• Poland
  • Kuyavian-Pomeranian Voivodeship
    • Bydgoszcz, Kuyavian-Pomeranian Voivodeship, Poland, 85-048
      • Recruiting
      • IN-VIVO Bydgoszcz
  • Wielkopolska
    • Poznan, Wielkopolska, Poland, 61731
      • Recruiting
      • Clinical Research Center Spółka z ograniczoną odpowiedzialnością Medic-R Sp.k.
  • Woj. Mazowieckie
    • Warsaw, Woj. Mazowieckie, Poland, 02798
      • Recruiting
      • Medical Concierge Centrum Medyczne
• South Korea
  • Gyeongsangnam-do
    • Yangsan, Gyeongsangnam-do, South Korea, 50612
      • Recruiting
      • Pusan National University Yangsan Hospital
  • Seoul
    • Seoul, Seoul, South Korea, 02841
      • Recruiting
      • Korea University Anam Hospital
    • Seoul, Seoul, South Korea, 06351
      • Recruiting
      • Samsung Medical Center
  • Songpa-gu
    • Seoul, Songpa-gu, South Korea, 03080
      • Recruiting
      • Seoul National University Hospital
• Spain
  • Málaga, Spain, 29010
    • Recruiting
    • Servicio Andaluz de Salud (SAS) - Hospital Universitario Virgen de la Victoria (HUVV)
  • Cantabria
    • Santander, Cantabria, Spain, 39008
      • Recruiting
      • Instituto de Investigacion Valdecilla (IDIVAL) / Hospital universitario Marques de Valdecilla
  • Catalonia
    • Barcelona, Catalonia, Spain, 08003
      • Recruiting
      • Hospital Del Mar
    • Barcelona, Catalonia, Spain, 08036
      • Recruiting
      • Hospital Clinic De Barcelona - University of Barcelona
  • Cordoba
    • Córdoba, Cordoba, Spain, 14004
      • Recruiting
      • Hospital Universitario Reina Sofia
  • Galicia
    • A Coruña, Galicia, Spain, 15006
      • Recruiting
      • Hospital Universitario de A Coruña
  • Madrid
    • Alcorcón, Madrid, Spain, 28922
      • Recruiting
      • Hospital Universitario Fundacion Alcorcon
    • Madrid, Madrid, Spain, 28027
      • Recruiting
      • Clínica Universidad de Navarra - Madrid
    • Madrid, Madrid, Spain, 28041
      • Recruiting
      • Hospital Universitario 12 de Octubre (Madrid)
    • Madrid, Madrid, Spain, 28046
      • Recruiting
      • Universidad Autonoma de Madrid. Hospital Universitario La Paz
  • Navarre
    • Pamplona, Navarre, Spain, 31008
      • Recruiting
      • Clinica Universidad de Navarra - Pamplona
  • Vizcaya
    • Bilbao, Vizcaya, Spain
      • Recruiting
      • Hospital Universitario Basurto
• United States
  • Arizona
    • Tucson, Arizona, United States, 85718
      • Recruiting
      • Center for Neurosciences
  • Arkansas
    • Little Rock, Arkansas, United States, 72211
      • Recruiting
      • Arkansas Urology, North Little Rock
  • California
    • Los Angeles, California, United States, 90017
      • Recruiting
      • American Institute of Research
    • Los Angeles, California, United States, 90080
      • Recruiting
      • USC Kenneth Norris Jr Cancer Hospital
    • Orange, California, United States, 92868
      • Recruiting
      • University of California, Irvine
    • San Diego, California, United States, 92123
      • Recruiting
      • Genesis Research, LLC - San Diego
  • Colorado
    • Denver, Colorado, United States, 80210
      • Recruiting
      • Advent Health
    • Lakewood, Colorado, United States, 80228
      • Recruiting
      • Colorado Urology - St. Anthony Hospital Campus
  • Connecticut
    • New Haven, Connecticut, United States, 06519
      • Recruiting
      • Yale School of Medicine
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20007
      • Recruiting
      • MedStar Georgetown University Hospital
  • Florida
    • Sarasota, Florida, United States, 34239
      • Recruiting
      • Sarasota Memorial Healthcare System
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Recruiting
      • Emory University
    • Atlanta, Georgia, United States, 30328
      • Recruiting
      • Georgia Urology
  • Idaho
    • Boise, Idaho, United States, 83702
      • Recruiting
      • Boise VA Medical Center
  • Illinois
    • Lisle, Illinois, United States, 60532
      • Recruiting
      • NextStage Clinical Research
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Recruiting
      • Indiana University
  • Kansas
    • Wichita, Kansas, United States, 67226
      • Recruiting
      • Wichita Urology Group
  • Maryland
    • Annapolis, Maryland, United States, 21401
      • Recruiting
      • Anne Arundel Urology, PA
    • Hanover, Maryland, United States, 21076
      • Recruiting
      • Chesapeake Urology Research Associates
  • New Jersey
    • Morristown, New Jersey, United States, 07960
      • Recruiting
      • Atlantic Health
  • New York
    • Buffalo, New York, United States, 14263
      • Recruiting
      • Roswell Park Cancer Institute
    • Cheektowaga, New York, United States, 14225
      • Recruiting
      • Great Lakes Physician PC d/b/a Western New York Urology Associates
    • Lake Success, New York, United States, 11042
      • Recruiting
      • Northwell Health -The Arthur Smith Institute for Urology
    • New York, New York, United States, 10010
      • Recruiting
      • Veterans Affairs New York Harbor Healthcare System - Manhattan VA Medical Center
    • The Bronx, New York, United States, 10468
      • Recruiting
      • James J. Peters VA Medical Center
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • Recruiting
      • University of Cincinnati
  • Pennsylvania
    • Bala-Cynwyd, Pennsylvania, United States, 19004
      • Recruiting
      • MidLantic Urology
    • Lancaster, Pennsylvania, United States, 17601
      • Recruiting
      • Keystone Urology Specialists
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • University of Pennsylvania - Perelman Center for Advanced Medicine - Penn Urology
    • Pittsburgh, Pennsylvania, United States, 15232
      • Recruiting
      • University of Pittsburgh Medical Center - Shadyside Medical Building
  • South Carolina
    • Myrtle Beach, South Carolina, United States, 29572
      • Recruiting
      • Carolina Urologic Research Center
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • Recruiting
      • The Conrad Pearson Clinic - Wolf River Office (Urology Center of the South)
    • Nashville, Tennessee, United States, 37209
      • Recruiting
      • Urology Associates, P.C.
  • Texas
    • Austin, Texas, United States, 78759
      • Recruiting
      • Urology Austin
    • Dallas, Texas, United States, 75231
      • Recruiting
      • Urology Clinics of North Texas PLLC (Dallas)
    • Dallas, Texas, United States, 75390
      • Recruiting
      • University of Texas Southwestern Medical Center - Urology Clinic
    • Houston, Texas, United States, 77030
      • Recruiting
      • Houston Methodist Hospital (Houston)
  • Washington
    • Seattle, Washington, United States, 98101
      • Recruiting
      • Virginia Mason Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 be willing to use a male condom and effective contraception during sex throughout the treatment period and for 3 months following the last dose.

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Nadofaragene firadenovec; Nadofaragene firadenovec (intravesical)	Drug: 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.; Other Names: ADSTILADRIN
Experimental: Nadofaragene firadenovec + gemcitabine & docetaxel; Nadofaragene firadenovec (intravesical), and sequential gemcitabine and docetaxel (intravesical)	Drug: 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.; Other Names: ADSTILADRIN; Drug: Gemcitabine; Intravesical Gemcitabine chemotherapy, used in combination with Docetaxel.; Drug: Docetaxel; Intravesical Docetaxel chemotherapy, used in combination with Gemcitabine.
Experimental: Nadofaragene firadenovec + Pembrolizumab; 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; 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.; Other Names: ADSTILADRIN; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete response	Complete response (CR) at any time from first treatment (defined as absence of high-grade (HG) recurrence).	up to 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Muscle-invasive progression of disease	Muscle-invasive progression of disease (defined as time from first treatment to first evidence of muscle-invasive disease or death)	up to 36 months
Cystectomy-free survival	Cystectomy-free survival (defined as time from first treatment to either cystectomy or death due to any cause)	up to 36 months
Adverse events	Adverse events collected for nadofaragene firadenovec in combination with chemotherapy (gemcitabine and docetaxel) or immunotherapy (pembrolizumab)	up to 36 months
Durability of complete response	Durability of complete response (defined as time from achieved CR to HG recurrence, progression or death due to any cause).	Up to 24 months
Overall survival	Overall survival (defined as time from first treatment to death due to any cause)	up to 36 months
Complete response at month 3	Complete response 3 months from first treatment	3 months
Complete response at month 6	Complete response 6 months from first treatment	6 months
Pathological staging	Pathological staging (tumor, node, metastasis staging system) in participants at time of cystectomy	up to 36 months
Evidence of malignant lesions of the upper tract and/or prostatic urethra	Evidence of malignant lesions of the upper tract and/or prostatic urethra (defined as time from first treatment to first evidence of malignant lesions).	up to 24 months

Collaborators and Investigators

• Sponsor: Ferring Pharmaceuticals
• Investigators: Study Director: Global Clinical Compliance, Ferring Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2024
• Primary Completion (Estimated): June 30, 2028
• Study Completion (Estimated): December 31, 2030

Study Registration Dates

• First Submitted: August 6, 2024
• First Submitted That Met QC Criteria: August 6, 2024
• First Posted (Actual): August 9, 2024

Study Record Updates

• Last Update Posted (Actual): May 22, 2026
• Last Update Submitted That Met QC Criteria: May 20, 2026
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Urologic Neoplasms; Carcinoma; Urinary Bladder Diseases; Non-Muscle Invasive Bladder Neoplasms; Carcinoma in Situ; Urinary Bladder Neoplasms; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Hydrocarbons; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Taxoids; Cyclodecanes; Diterpenes; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Docetaxel; Gemcitabine; pembrolizumab
• Other Study ID Numbers: 000434; U1111-1299-0176 (Other Identifier: World Health Organization)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No