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

Trial Summary

What is the purpose of this trial?

The purpose of this study is to compare the effectiveness of different FDA-approved/NCCN-recommended drug treatments for NMIBC. In particular, the FDA-approved drug nadofaragene firadenovec will be compared to usual care with other NCCN-recommended standard treatments for NMIBC (gemcitabine with or without docetaxel, mitomycin, re-treatment with BCG, or pembrolizumab).

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.

What data supports the effectiveness of the drug Nadofaragene Firadenovec in treating bladder cancer?

Research shows that gemcitabine, one of the drugs used in the trial, has been effective in treating bladder cancer, with response rates of 23% to 28% when used alone and up to 66% when combined with cisplatin. This suggests that gemcitabine, as part of the treatment, may contribute to its effectiveness in bladder cancer. ^{1 2 3 4 5}

Is Nadofaragene Firadenovec safe for humans?

Nadofaragene Firadenovec is a gene therapy approved for treating certain types of bladder cancer, and its safety has been evaluated in clinical settings. It is designed to produce a protein that helps fight cancer, and while it has shown anticancer activity, like any treatment, it may have side effects that should be discussed with a healthcare provider. ^{2 5 6 7 8}

How is the treatment Nadofaragene Firadenovec different from standard 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 standard chemotherapy drugs like Docetaxel and Gemcitabine, which work by killing cancer cells directly. ^{8 9 10 11 12}

Research Team

Eugene Pietzak, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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 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]

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, 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]

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 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]

References

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

Weekly paclitaxel and gemcitabine in advanced transitional-cell carcinoma of the urothelium: a phase II Hoosier Oncology Group study. [2022]

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

An evaluation of monthly maintenance therapy among patients receiving intravesical combination gemcitabine/docetaxel for nonmuscle-invasive bladder cancer. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Gemcitabine in the treatment of bladder cancer. [2022]

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

Gemcitabine in bladder cancer. [2022]

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

Intravesical gemcitabine therapy for superficial transitional cell carcinoma of the bladder: a phase I and pharmacokinetic study. [2022]

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

Cisplatin, gemcitabine, and ifosfamide as weekly therapy: a feasibility and phase II study of salvage treatment for advanced transitional-cell carcinoma. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Gemcitabine and docetaxel as first-line treatment for advanced urothelial carcinoma: a phase II study. [2022]

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

Nadofaragene Firadenovec: First Approval. [2023]

9. Switzerland pubmed.ncbi.nlm.nih.gov

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

10. 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]

11. 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]

12. Netherlands 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. [2022]