Nadofaragene Firadenovec for Bladder Cancer

(ABLE-22 Trial)

Recruiting at 8 trial locations

Overseen By Global Clinical Compliance

Age: 18+

Sex: Any

Trial Phase: Phase 2

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)

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

150 Participants Needed

Trial Summary

What is the purpose of this trial?

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).

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.

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

Research shows that Nadofaragene Firadenovec, a gene therapy, has shown promising results in treating bladder cancer that doesn't respond to BCG treatment. Clinical trials reported high response rates and manageable side effects, and a phase 3 trial found that certain antibody levels could predict the durability of the treatment's effectiveness. ^{1 2 3 4 5}

Is Nadofaragene Firadenovec safe for humans?

Clinical trials for Nadofaragene Firadenovec, a gene therapy for bladder cancer, have shown promising results with high response rates and manageable side effects, indicating it is generally safe for human use. ^{1 2 3 4 6}

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, specifically for patients who do not respond to BCG treatment. It works by delivering a gene into the bladder cells that produces interferon, a protein that helps fight cancer, making it a novel approach compared to traditional treatments. ^{1 2 3 4 6}

Research Team

Global Clinical Compliance

Principal Investigator

Ferring Pharmaceuticals

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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 gemcitabine and docetaxel (intravesical)

Group III: Nadofaragene firadenovec Experimental Treatment 1 Intervention

Intravesical treatment with nadofaragene firadenovec only

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

Findings from Research

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]

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]

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, 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]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

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

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

Nadofaragene Firadenovec: First Approval. [2023]

3. 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]

4. 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]

5. 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]

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]