Nadofaragene Firadenovec vs Standard Treatments for Bladder Cancer

Overseen By Eugene Pietzak, MD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Memorial Sloan Kettering Cancer Center

Must be taking: Intravesical agents

Disqualifiers: Radical cystectomy, Experimental therapy, 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

Compensation: Varies

Number of Visits: Unknown

Duration: 24 months

125 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of nadofaragene firadenovec compared to standard treatments for non-muscle invasive bladder cancer (NMIBC). Researchers aim to determine if this new drug surpasses usual care options such as gemcitabine, docetaxel, mitomycin, BCG re-treatment, or pembrolizumab. Individuals with high-grade NMIBC who previously received ineffective BCG treatment may be suitable candidates for this trial. Participants will either receive the experimental treatment or continue with the best usual care as determined by their doctor. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to the potential availability of a new treatment option.

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 this trial's treatments are likely to be safe?

Research has shown that nadofaragene firadenovec is usually well-tolerated. Most side effects are mild, such as tiredness and fever. One study found that only 9% of patients experienced more serious side effects, including severe tiredness, fever, or dizziness. Importantly, the study reported no life-threatening side effects. This suggests that nadofaragene firadenovec is relatively safe for use. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Most treatments for bladder cancer, like Docetaxel and Gemcitabine, focus on killing cancer cells through chemotherapy. However, Nadofaragene Firadenovec stands out because it uses gene therapy to fight the disease. This treatment delivers a specific gene into bladder cells, prompting them to produce a protein that boosts the immune system's ability to attack cancer cells. Researchers are excited about this innovative approach because it offers a new way to potentially enhance the body's natural defenses against cancer, which could lead to more effective and longer-lasting results.

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

Research has shown that nadofaragene firadenovec, one of the treatments tested in this trial, holds promise for treating non-muscle invasive bladder cancer (NMIBC). In studies, 79% of patients with carcinoma in situ, a specific type of bladder cancer, were cancer-free after three months. Furthermore, 84% of these patients remained cancer-free for an extended period. This suggests effectiveness, particularly for those unresponsive to BCG treatment. Real-world evidence supports these findings, demonstrating high tumor clearance rates and a good safety record. Participants in this trial may receive either nadofaragene firadenovec or the standard treatment, which includes intravesical GemDoce. ^{2 3 5 6 7}

Who Is on the Research Team?

Eugene Pietzak, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for individuals with Non-Muscle Invasive Bladder Cancer (NMIBC). Participants should be eligible for standard treatments and have not responded well to previous therapies. Specific eligibility criteria are not provided, but typically include factors like age, cancer stage, and overall health.

Inclusion Criteria

I am 21 years old or older.

I am being treated for a specific type of bladder cancer at MSK.

I have had BCG treatment for bladder cancer that didn't work.

Exclusion Criteria

Currently enrolled in a clinical trial of an experimental therapy for NMIBC

I am choosing to have my bladder removed.

I have been treated with nadofaragene firadenovec before.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either nadofaragene firadenovec or best usual care with intravesical GemDoce

24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Docetaxel
• Gemcitabine
• Nadofaragene Firadenovec

Trial Overview The study compares the effectiveness of nadofaragene firadenovec—an FDA-approved drug—against other NCCN-recommended treatments such as gemcitabine with or without docetaxel, mitomycin, re-treatment with BCG, or pembrolizumab in treating NMIBC.

How Is the Trial Designed?

Group I: Nadofaragene firadenovec Experimental Treatment 1 Intervention

The patient will receive nadofaragene firadenovec.

Group II: Best usual care Active Control 2 Interventions

For patients randomized to receive best usual care, the combination of intravesical GemDoce is the current standard of care at MSK for most patients with BCG failure.

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Published Research Related to This Trial

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 II trial involving 36 patients with advanced transitional-cell carcinoma, the combination of weekly paclitaxel and gemcitabine showed a significant response rate, with 69.4% of patients achieving major responses, including 41.7% with complete responses.

Despite its efficacy, the treatment was associated with a concerning incidence of pulmonary toxicity, leading to a recommendation against its use due to safety concerns, particularly after observing severe toxicities in some patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Weekly paclitaxel and gemcitabine in advanced transitional-cell carcinoma of the urothelium: a phase II Hoosier Oncology Group study. Li, J., Juliar, B., Yiannoutsos, C., et al.[2022]

Gemcitabine, a newer chemotherapy agent, has shown promising activity against bladder cancer, both as a single agent and in combination with cisplatin, offering a favorable toxicity profile compared to traditional treatments.

The standard treatment for advanced bladder cancer in the US remains the M-VAC regimen, but ongoing trials are exploring the effectiveness of gemcitabine combined with other agents, which may lead to improved treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine in the treatment of bladder cancer. Ryan, CW., Vogelzang, NJ.[2022]

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]

In a study of 59 patients with nonmuscle-invasive bladder cancer treated with intravesical gemcitabine/docetaxel (GEM/DOCE), the overall disease-free survival (DFS) was 49% at 1 year and 29% at 2 years, indicating that GEM/DOCE is a viable treatment option, especially for those who have failed previous therapies.

Patients who received monthly maintenance therapy after an initial complete response to GEM/DOCE had significantly better DFS rates (81% at 1 year) compared to those who were only observed (42% at 1 year), suggesting that maintenance therapy enhances long-term outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An evaluation of monthly maintenance therapy among patients receiving intravesical combination gemcitabine/docetaxel for nonmuscle-invasive bladder cancer. Daniels, MJ., Barry, E., Milbar, N., et al.[2022]

The combination of docetaxel and gemcitabine offers a promising second-line treatment option for patients with non-muscle-invasive bladder cancer that does not respond to bacillus Calmette-Guérin therapy.

Both drugs are well tolerated as individual treatments and have different mechanisms of action, making their combination a potentially effective and affordable standard of care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sequential Gemcitabine plus Docetaxel Is the Standard Second-line Intravesical Therapy for BCG-unresponsive Non-muscle-invasive bladder cancer: Pro. Roumiguié, M., Black, PC.[2022]

The combination of gemcitabine and docetaxel showed a 51.6% overall response rate in 31 patients with advanced urothelial carcinoma, indicating significant efficacy as a first-line treatment.

The treatment was well tolerated, with manageable hematologic toxicities and no toxic deaths, suggesting it could be a safer alternative for patients with compromised renal function or cardiovascular issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine and docetaxel as first-line treatment for advanced urothelial carcinoma: a phase II study. Ardavanis, A., Tryfonopoulos, D., Alexopoulos, A., 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]

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. 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.

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. 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.

5. onclive.com onclive.com/view/efficacy-and-safety-of-nadofaragene-firadenovec-hold-up-in-nmibc-real-world-study

Efficacy and Safety of Nadofaragene Firadenovec Hold Up ... Nadofaragene firadenovec showed a 79% complete response rate at 3 months in patients with carcinoma in situ, with 84% maintaining response at ...

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. 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 ...