Nadofaragene Firadenovec for Bladder Cancer

(ABLE-32 Trial)

Recruiting at 23 trial locations

Overseen By Global Clinical Compliance

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?

A phase 3b, Randomized, Controlled Trial of Nadofaragene Firadenovec vs. Observation in Participants with Intermediate Risk Non-Muscle Invasive Bladder Cancer (IR NMIBC)

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 Nadofaragene Firadenovec safe for humans?

Clinical trials for Nadofaragene Firadenovec, a gene therapy for bladder cancer, have shown promising results with manageable side effects. This means that while some side effects may occur, they are generally not severe and can be controlled. ^{1 2 3 4 5}

How is the treatment Nadofaragene Firadenovec different from other treatments for bladder cancer?

Nadofaragene Firadenovec is unique because it is the first gene therapy approved for bladder cancer, using a modified virus to deliver a gene that produces interferon (a protein that helps fight cancer) directly into the bladder. This approach is different from traditional treatments as it directly modifies the bladder cells to produce cancer-fighting proteins. ^{1 2 3 4 5}

What data supports the effectiveness of the treatment Nadofaragene Firadenovec for bladder cancer?

Nadofaragene Firadenovec has shown promising results in clinical trials for patients with bladder cancer who do not respond to BCG treatment. A phase 3 trial reported a high complete response rate, and the treatment was approved in the USA for high-risk non-muscle-invasive bladder cancer, indicating its effectiveness. ^{1 3 4 5 6}

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

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]

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]

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 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. England 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. [2022]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Interferon gene therapy with nadofaragene firadenovec for bladder cancer: from bench to approval. [2023]

3. United States 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. [2022]

4. New Zealand pubmed.ncbi.nlm.nih.gov

Nadofaragene Firadenovec: First Approval. [2023]

5. Switzerland 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. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Cost-Effectiveness of Nadofaragene Firadenovec and Pembrolizumab in Bacillus Calmette-Guérin Immunotherapy Unresponsive Non-Muscle Invasive Bladder Cancer. [2023]