Recruiting
Phase 3

Nadofaragene Firadenovec, Chemotherapy, Immunotherapy

Sponsor:

Ferring Pharmaceuticals

Code:

NCT06545955

Conditions

Non-muscle Invasive Bladder Cancer With Carcinoma in Situ

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Nadofaragene Firadenovec

Gemcitabine

Docetaxel

Pembrolizumab

Study Details

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

Study ID

NCT06545955

Start date

Oct 1, 2024

Status verified date

Nov, 2025

Completion date

Dec 31, 2030

Anticipated

Primary completion date

Jun 30, 2028

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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 Design

Enrollment

250 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Nadofaragene firadenovec

Nadofaragene firadenovec (intravesical)

experimental: Nadofaragene firadenovec + gemcitabine & docetaxel

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

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.

Interventions

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.

Gemcitabine

Intravesical Gemcitabine chemotherapy, used in combination with Docetaxel.

Docetaxel

Intravesical Docetaxel chemotherapy, used in combination with Gemcitabine.

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.

Primary outcome measure

  • Complete response [ Time Frame: up to 6 months ]

Central Contacts and Locations

Central contacts

Ferring Pharmaceuticals

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

Ferring Pharmaceuticals

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

Locations

Center for Neurosciences

Recruiting

Tucson, Arizona, United States, 85718

Arkansas Urology, North Little Rock

Recruiting

Little Rock, Arkansas, United States, 72211

American Institute of Research

Recruiting

Los Angeles, California, United States, 90017

USC Kenneth Norris Jr Cancer Hospital

Recruiting

Los Angeles, California, United States, 90080

University of California, Irvine

Recruiting

Orange, California, United States, 92868

Genesis Research, LLC - San Diego

Recruiting

San Diego, California, United States, 92123

Advent Health

Recruiting

Denver, Colorado, United States, 80210

Colorado Urology - St. Anthony Hospital Campus

Recruiting

Lakewood, Colorado, United States, 80228

Yale School of Medicine

Recruiting

New Haven, Connecticut, United States, 06519

Medstar Georgetown University Hospital

Recruiting

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

Sarasota Memorial Healthcare System

Recruiting

Sarasota, Florida, United States, 34239

Emory University

Recruiting

Atlanta, Georgia, United States, 30322

Georgia Urology

Recruiting

Atlanta, Georgia, United States, 30328

Boise VA Medical Center

Recruiting

Boise, Idaho, United States, 83702

NextStage Clinical Research

Recruiting

Lisle, Illinois, United States, 60532

Indiana University

Recruiting

Indianapolis, Indiana, United States, 46202

Wichita Urology Group

Recruiting

Wichita, Kansas, United States, 67226

Anne Arundel Urology, PA

Recruiting

Annapolis, Maryland, United States, 21401

Chesapeake Urology Research Associates

Recruiting

Hanover, Maryland, United States, 21076

Atlantic Health

Recruiting

Morristown, New Jersey, United States, 07960

Roswell Park Cancer Institute

Recruiting

Buffalo, New York, United States, 14263

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

Recruiting

Cheektowaga, New York, United States, 14225

Northwell Health -The Arthur Smith Institute for Urology

Recruiting

Lake Success, New York, United States, 11042

Veterans Affairs New York Harbor Healthcare System - Manhattan VA Medical Center

Recruiting

New York, New York, United States, 10010

James J. Peters VA Medical Center

Recruiting

The Bronx, New York, United States, 10468

University of Cincinnati

Recruiting

Cincinnati, Ohio, United States, 45267

OSU Arthur James Cancer Hospital

Recruiting

Columbus, Ohio, United States, 43201

MidLantic Urology

Recruiting

Bala-Cynwyd, Pennsylvania, United States, 19004

Keystone Urology Specialists

Recruiting

Lancaster, Pennsylvania, United States, 17601

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

Recruiting

Philadelphia, Pennsylvania, United States, 19104

University of Pittsburgh Medical Center - Shadyside Medical Building

Recruiting

Pittsburgh, Pennsylvania, United States, 15232

Carolina Urologic Research Center

Recruiting

Myrtle Beach, South Carolina, United States, 29572

The Conrad Pearson Clinic - Wolf River Office (Urology Center of the South)

Recruiting

Germantown, Tennessee, United States, 38138

Urology Associates, P.C.

Recruiting

Nashville, Tennessee, United States, 37209

Urology Austin

Recruiting

Austin, Texas, United States, 78759

Urology Clinics of North Texas PLLC (Dallas)

Recruiting

Dallas, Texas, United States, 75231

University of Texas Southwestern Medical Center - Urology Clinic

Recruiting

Dallas, Texas, United States, 75390

Houston Methodist Hospital (Houston)

Recruiting

Houston, Texas, United States, 77030

Virginia Mason Medical Center

Recruiting

Seattle, Washington, United States, 98101

Prostate Cancer Centre

Recruiting

Calgary, Alberta, Canada, T2V 1P9

University Health Network UHN - Princess Margaret Cancer Centre

Recruiting

Toronto, Ontario, Canada, M5G 1Z5

Centre Hospitalier de L'Universite de Montreal

Recruiting

Montreal, Quebec, Canada, H2X 0A9

More Information

Sponsor

Ferring Pharmaceuticals

Last update posted

Aug 6, 2026

Last verified

Nov, 2025

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by Ferring Pharmaceuticals on 2026-08-06.