Nadofaragene Firadenovec for Bladder Cancer

(ABLE-22 Trial)

Recruiting at 50 trial locations

Overseen By Ferring Pharmaceuticals

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Ferring Pharmaceuticals

Must not be taking: Systemic therapy, Intravesical chemotherapy

Disqualifiers: Muscle-invasive disease, Metastatic disease, 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: 12 months

250 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effectiveness of a new treatment called nadofaragene firadenovec for individuals with a specific type of bladder cancer that hasn't responded to standard treatment. The trial will assess how well this treatment works alone and in combination with other drugs like chemotherapy or immunotherapy. It seeks participants with non-muscle invasive bladder cancer that didn't improve after at least two rounds of Bacillus Calmette-Guerin (BCG) therapy. Participants should not show any signs of more advanced cancer that has spread to muscles or other parts of the body. 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 protocol does not specify whether you need to stop taking your current medications. However, if you are currently on systemic therapy for bladder cancer or have had prior investigational treatments for BCG-unresponsive NMIBC, you may not be eligible to participate.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that nadofaragene firadenovec is generally safe and well-tolerated. Most side effects are mild, such as tiredness and fever. Only a small number (9%) of patients experienced more serious issues like tiredness, fever, and dizziness, but no life-threatening side effects were reported.

For those considering combining it with gemcitabine and docetaxel, or with pembrolizumab, it is important to note that nadofaragene firadenovec is already approved for treating bladder cancer. This approval provides additional confidence in its safety. While this trial examines its use with other treatments, the existing approval indicates that nadofaragene firadenovec is known to be safe on its own. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Nadofaragene Firadenovec for bladder cancer because it uses a unique virus-based gene therapy approach. Unlike standard treatments like BCG therapy, Nadofaragene Firadenovec introduces a modified virus directly into the bladder to deliver a gene that boosts the body’s immune response against cancer cells. In one arm, it’s combined with gemcitabine and docetaxel, enhancing its delivery and efficacy. Another arm pairs it with pembrolizumab, an immune checkpoint inhibitor, potentially offering a powerful dual approach to attacking cancer cells. This innovative delivery and mechanism of action provide a fresh hope for more effective treatments against bladder cancer.

What evidence suggests that this trial's treatments could be effective for bladder cancer?

In this trial, participants will receive different treatment combinations involving nadofaragene firadenovec. A previous study showed a 53.4% complete response rate in patients with bladder cancer, meaning more than half of the patients had no signs of cancer after treatment. Real-world data supports these findings, indicating high success rates and general safety. One arm of this trial will test nadofaragene firadenovec with chemotherapy drugs like gemcitabine and docetaxel, which remains a promising option. Another arm will combine it with pembrolizumab, an immunotherapy, which has shown similar positive results. Overall, strong evidence suggests that nadofaragene firadenovec is effective for treating non-muscle invasive bladder cancer. ^{2 3 5 6 7}

Who Is on the Research Team?

Global Clinical Compliance

Principal Investigator

Ferring Pharmaceuticals

Are You a Good Fit for This Trial?

This trial is for people with high-grade non-muscle invasive bladder cancer who haven't responded to BCG therapy. They should have had at least two courses of BCG in the past year and all visible tumors must be removed before starting the trial. Those with T1 disease need an additional check to confirm no progression.

Inclusion Criteria

I have been diagnosed with early-stage, high-grade cancer.

I have no limit on the BCG treatment I can receive.

I have had all visible bladder tumors removed and, if needed, underwent a second surgery within 14 to 70 days before starting the trial.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive intravesical nadofaragene firadenovec alone or in combination with chemotherapy or immunotherapy

12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

Long-term follow-up

Participants are monitored for overall survival and adverse events

36 months

What Are the Treatments Tested in This Trial?

Interventions

• Docetaxel
• Gemcitabine
• Nadofaragene Firadenovec
• Pembrolizumab

Trial Overview The study tests nadofaragene firadenovec, a gene therapy, alone or combined with chemotherapy drugs Gemcitabine or Docetaxel, or immunotherapy Pembrolizumab. It aims to see how well these treatments work for bladder cancer that didn't improve after BCG treatment.

How Is the Trial Designed?

Group I: Nadofaragene firadenovec + pembrolizumab Experimental Treatment 2 Interventions

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

Group II: Nadofaragene firadenovec + gemcitabine & docetaxel Experimental Treatment 3 Interventions

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

Group III: Nadofaragene firadenovec Experimental Treatment 1 Intervention

Nadofaragene firadenovec (intravesical)

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]

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]

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]

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]

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, ... The most common outcomes reported in the pivotal trials were complete response (CR) and high-grade recurrence free survival (HGRFS) at prespecified time points ...

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® ... The study is evaluating complete response rates, high-grade recurrence-free survival, cystectomy-free survival, overall survival, and adverse events.

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

Efficacy: REAL-WORLD evidence Real-world results · At a median follow-up of 8.2 months, CFS and OS were 95% and 100%, respectively · 3 patients experienced progression: 1 from Ta to T1, 1 from ...

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

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

7. 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.