Nadofaragene Firadenovec for Bladder Cancer

(ABLE-32 Trial)

Recruiting at 70 trial locations

Overseen By Ferring Pharmaceuticals

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Ferring Pharmaceuticals

Disqualifiers: Muscle invasive, Metastatic, High risk, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 24 months

454 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called Nadofaragene Firadenovec for individuals with a specific type of bladder cancer that hasn't spread to the muscles. The goal is to determine if this treatment can manage or reduce the cancer more effectively than monitoring the condition alone. Some participants will receive the treatment, while others will be closely observed without active treatment to compare outcomes. Suitable candidates have experienced bladder cancer recurrence within a year or have small tumors that haven't invaded nearby muscles. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that Nadofaragene Firadenovec is likely to be safe for humans?

Research has shown that nadofaragene firadenovec is generally safe and well-tolerated. Patients who received this treatment reported handling it without major problems. Early real-world data, examining how treatments work outside controlled studies, also supports its safety. This treatment has been used for patients with a type of bladder cancer, particularly those who did not respond to BCG therapy. These findings suggest that nadofaragene firadenovec is generally safe for use in humans. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for bladder cancer?

Nadofaragene firadenovec is unique because it uses a gene therapy approach to treat bladder cancer. Unlike traditional treatments like surgery, chemotherapy, or BCG (Bacillus Calmette-Guérin) therapy, this treatment involves delivering a virus carrying a gene directly into the bladder cells. This gene then prompts the cells to produce a protein that stimulates the immune system to attack cancer cells. Researchers are excited about nadofaragene firadenovec because it offers a new, potentially less invasive way to harness the body's immune response to fight the cancer, which could lead to improved outcomes for patients.

What evidence suggests that Nadofaragene Firadenovec might be an effective treatment for bladder cancer?

Research has shown that nadofaragene firadenovec, which participants in this trial may receive, holds promise for treating bladder cancer. Studies have found that it leads to high rates of complete response in patients unresponsive to BCG, a common treatment. Many patients showed no signs of cancer after treatment. It is generally well-tolerated, indicating a favorable safety profile. Additionally, its effectiveness matches or surpasses current treatments. These findings suggest nadofaragene firadenovec could be a valuable option for people with bladder cancer. ^{2 3 6 7 8}

Who Is on the Research Team?

Global Clinical Compliance

Principal Investigator

Ferring Pharmaceutical

Are You a Good Fit for This Trial?

This trial is for people with a type of bladder cancer that hasn't spread into muscle. They should have had a recurrence within a year or have certain sizes and grades of tumors as per AUA/SUO guidelines. It's not specified who can't join, but typically there would be criteria excluding those with advanced disease or poor health.

Inclusion Criteria

I have been diagnosed with a type of bladder cancer that is not in the muscle and is considered intermediate risk.

My low-grade Ta cancer has come back within a year.

My bladder cancer is low-grade and the tumor is larger than 3 cm.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants in the nadofaragene firadenovec arm will receive quarterly instillations with nadofaragene firadenovec for 24 months. Observation arm subjects will be followed based on the surveillance schedule of the AUA/SUO guideline (quarterly) over the 24 months treatment period.

24 months

Quarterly visits

Follow-up

Participants are monitored for recurrence-free survival and adverse events up to 24 months

24 months

What Are the Treatments Tested in This Trial?

Interventions

• Nadofaragene Firadenovec

Trial Overview The study is testing Nadofaragene Firadenovec, which is likely a new treatment for bladder cancer. Participants are randomly chosen to either receive this treatment or just be observed without it to compare outcomes.

How Is the Trial Designed?

Group I: Arm 1 Nadofaragene Firadenovec Experimental Treatment 1 Intervention

Participants in the nadofaragene firadenovec arm will receive quarterly instillations with nadofaragene firadenovec for 24 months. For these subjects, the disease evaluation visits will occur within 2 weeks prior to the investigation medicinal products instillation visits.

Group II: Arm 2 - Observation Active Control 1 Intervention

Subjects will be followed based on the surveillance schedule of the AUA/SUO guideline (quarterly) over the 24 months treatment period. .

Nadofaragene Firadenovec is already approved in United States for the following indications:

Approved in United States as Adstiladrin for:

• High-risk Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors

Who Is Running the Clinical Trial?

Ferring Pharmaceuticals

Lead Sponsor

Trials

323

Recruited

1,242,000+

Pierre-Yves Berclaz

Ferring Pharmaceuticals

Chief Medical Officer since 2023

MD from the University of Lausanne, PhD in Molecular Biology from the Cincinnati College of Medicine

Jean-Frédéric Paulsen

Ferring Pharmaceuticals

Chief Executive Officer since 2023

Master’s degree in Finance from the London School of Economics and Political Science

Published Research Related to This Trial

Nadofaragene firadenovec (Adstiladrin®) is the first gene therapy approved for bladder cancer, offering a new treatment option for patients who do not respond to Bacillus Calmette-Guérin (BCG) therapy.

Clinical trials have demonstrated high response rates and manageable side effects for nadofaragene firadenovec, indicating its potential as an effective alternative in treating bladder cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interferon gene therapy with nadofaragene firadenovec for bladder cancer: from bench to approval. Martini, A., Tholomier, C., Mokkapati, S., et al.[2023]

Nadofaragene firadenovec is the first approved gene therapy for treating high-risk BCG-unresponsive non-muscle invasive bladder cancer, specifically targeting carcinoma in situ and papillary tumors.

This therapy works by using an adenoviral vector to deliver DNA that encodes interferon (IFN)-α2b, which helps fight cancer through immunostimulatory, antiangiogenic, and apoptotic effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nadofaragene Firadenovec: First Approval. Lee, A.[2023]

In a phase 3 study involving 157 patients with BCG-unresponsive non-muscle-invasive bladder cancer, 53.4% of patients with carcinoma in situ achieved a complete response within 3 months of receiving nadofaragene firadenovec, with 45.5% maintaining this response at 12 months.

The treatment demonstrated a favorable safety profile, with only mild to moderate adverse events reported, such as micturition urgency, and no treatment-related deaths, indicating a good benefit-to-risk ratio for this novel therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravesical nadofaragene firadenovec gene therapy for BCG-unresponsive non-muscle-invasive bladder cancer: a single-arm, open-label, repeat-dose clinical trial. Boorjian, SA., Alemozaffar, M., Konety, BR., et al.[2022]

The phase I trial of intravesical recombinant adenovirus-mediated interferon-α2b gene therapy (rAd-IFNα) was well tolerated in 17 patients with recurrent nonmuscle invasive bladder cancer, showing no dose-limiting toxicity and only mild adverse events, primarily urgency.

At 3 months, 43% of patients treated with higher doses of rAd-IFNα achieved a complete response, indicating promising preliminary efficacy of this gene therapy in managing bladder cancer recurrence after previous treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I trial of intravesical recombinant adenovirus mediated interferon-α2b formulated in Syn3 for Bacillus Calmette-Guérin failures in nonmuscle invasive bladder cancer. Dinney, CP., Fisher, MB., Navai, N., et al.[2022]

In a phase 3 trial involving 91 patients with BCG-unresponsive non-muscle-invasive bladder cancer, the intravesical treatment nadofaragene firadenovec showed a promising complete response rate, with 52% of patients remaining recurrence-free at 12 months.

Serum antiadenovirus antibody levels, particularly post-treatment titers greater than 800, were found to be predictive of durable treatment response, suggesting that monitoring these antibody levels could help assess the effectiveness of nadofaragene firadenovec in future treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antiadenovirus Antibodies Predict Response Durability to Nadofaragene Firadenovec Therapy in BCG-unresponsive Non-muscle-invasive Bladder Cancer: Secondary Analysis of a Phase 3 Clinical Trial. Mitra, AP., Narayan, VM., Mokkapati, S., et al.[2023]

Nadofaragene firadenovec, a gene therapy for BCG-unresponsive non-muscle-invasive bladder cancer, showed an incremental cost-effectiveness ratio of $263,000 per QALY in carcinoma in situ (CIS) and $145,000 in non-CIS populations, indicating it may not be cost-effective unless priced lower.

Pembrolizumab, while having a higher cost-effectiveness ratio of $168,000 per QALY for CIS, could become cost-effective with a 5.4% price reduction, highlighting its potential as an important treatment option in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-Effectiveness of Nadofaragene Firadenovec and Pembrolizumab in Bacillus Calmette-Guérin Immunotherapy Unresponsive Non-Muscle Invasive Bladder Cancer. Joshi, M., Atlas, SJ., Beinfeld, M., et al.[2023]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.5_suppl.716

Real-world outcomes of nadofaragene firadenovec in BCG ... Early real-world data demonstrates encouraging clinical complete response rates in patients with BCG-unresponsive NMIBC and a favorable safety profile.

2. ferringusa.com ferringusa.com/?press=first-real-world-outcomes-data-for-adstiladrin-nadofaragene-firadenovec-vncg-to-be-presented-at-2025-asco-genitourinary-cancers-symposium

First Real-World Outcomes Data for ADSTILADRIN ... The study is evaluating complete response rates, high-grade recurrence-free survival, cystectomy-free survival, overall survival, and adverse events.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10391138/

The effectiveness and value of nadofaragene firadenovec, ... Although outcomes of nadofaragene firadenovec and oportuzumab monatox show response rates that are similar to or better than currently available treatments, ...

4. urotoday.com urotoday.com/conference-highlights/asco-gu-2025/asco-gu-2025-press-releases/158114-first-real-world-outcomes-data-for-adstiladrin-nadofaragene-firadenovec-vncg-to-be-presented-at-2025-asco-genitourinary-cancers-symposium.html

First Real-World Outcomes Data for ADSTILADRIN® ... Independent experience at three Mayo Clinic sites and real-world outcomes data with ADSTILADRIN in patients with high-risk Bacillus Calmette-Guérin ...

5. adstiladrinhcp.com adstiladrinhcp.com/real-world-evidence/

Efficacy: REAL-WORLD evidence Patients with BCG-unresponsive NMIBC treated with ADSTILADRIN were retrospectively analyzed at 3 Mayo Clinic sites from November 2023 to December 2024.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40194933/

Safety of nadofaragene firadenovec-vncg: review of data ... Nadofaragene firadenovec demonstrated a favorable and tolerable safety profile across its clinical study program, allowing for broad patient selection.

7. ferringusa.com ferringusa.com/?press=ferring-highlights-new-real-world-research-with-adstiladrin-nadofaragene-firadenovec-vncg-in-clinical-practice

Ferring Highlights New Real-World Research with ... ABLE-41, a real-world evidence study for bladder cancer patients treated with nadofaragene firadenovec: baseline patient characteristics and ...

8. urotoday.com urotoday.com/conference-highlights/asco-gu-2025/asco-gu-2025-bladder-cancer/158308-asco-gu-2025-real-world-outcomes-of-nadofaragene-firadenovec-in-bcg-unresponsive-nmibc.html

ASCO GU 2025: Real-World Outcomes of Nadofaragene ... This study analyzed patients treated with nadofaragene firadenovec for BCG-unresponsive non-muscle invasive bladder cancer across three Mayo Clinic sites.