Nadofaragene Firadenovec + Standard Therapy for Bladder Cancer

(TRIFECTA Trial)

JW
Overseen ByJonathan Wright, MD
Age: 18+
Sex: Any
Trial Phase: Phase 2
Sponsor: University of Washington
Must be taking: Cisplatin, Gemcitabine, Durvalumab
Stay on Your Current MedsYou can continue your current medications while participating
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment combination for people with muscle-invasive bladder cancer. Researchers aim to determine if adding the gene therapy nadofaragene firadenovec to standard chemotherapy and immunotherapy improves outcomes. The goal is to assess the safety and effectiveness of this combination before bladder removal surgery. Individuals with muscle-invasive bladder cancer scheduled for surgery might be suitable candidates for this trial. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group of participants.

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

Research has shown that nadofaragene firadenovec is generally safe. Studies on patients with non-muscle invasive bladder cancer found it well-tolerated, with many patients experiencing no serious side effects. The FDA has already approved this treatment for this type of bladder cancer, indicating its general safety.

The other treatments in this trial—gemcitabine, cisplatin, and durvalumab—are commonly used for bladder cancer and have established safety records. Combining these with nadofaragene firadenovec aims to improve results while maintaining safety.12345

Why are researchers excited about this study treatment for bladder cancer?

Nadofaragene firadenovec is unique because it uses a novel gene therapy approach to treat bladder cancer. Unlike traditional treatments like surgery, chemotherapy, and immunotherapy, this treatment delivers a virus directly into the bladder, introducing a gene that helps the body's own immune system to fight cancer cells. Researchers are excited because this method has the potential to enhance the body's natural defenses specifically within the bladder, offering a targeted approach that could lead to fewer side effects and improved effectiveness compared to current options.

What evidence suggests that nadofaragene firadenovec combined with standard therapy could be effective for muscle invasive bladder cancer?

Research has shown that nadofaragene firadenovec effectively treats non-muscle invasive bladder cancer. In earlier studies, nearly half of the patients who received this treatment retained their bladder for up to 60 months. This treatment uses a virus to deliver a gene that produces interferon alfa-2b, a substance that helps destroy cancer cells. The therapy is administered directly into the bladder, targeting the cancer's location. In this trial, researchers are testing nadofaragene firadenovec alongside standard treatments, including durvalumab, gemcitabine, and cisplatin, to evaluate its potential benefits for those with muscle invasive bladder cancer.13467

Who Is on the Research Team?

JW

Jonathan Wright, MD

Principal Investigator

Fred Hutch/University of Washington Cancer Consortium

Are You a Good Fit for This Trial?

This trial is for patients with muscle invasive bladder cancer who are candidates for radical cystectomy. It's testing if adding nadofaragene firadenovec to the standard chemo and immunotherapy regimen before surgery can improve outcomes.

Inclusion Criteria

Platelet count of ≥ 100,000/uL
My bladder cancer is mainly urothelial type.
Hemoglobin count ≥ 9 gm/dL
See 11 more

Exclusion Criteria

I have been treated with adenovirus-based drugs before.
Pregnant or lactating women
My cancer is at an advanced stage, affecting nearby lymph nodes or other parts of my body.
See 6 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Treatment

Participants receive durvalumab, gemcitabine, cisplatin, and nadofaragene firadenovec. Cycles repeat every 21 days for up to 4 cycles.

12 weeks
4 cycles with multiple visits per cycle

Radical Cystectomy (RC)

Participants undergo radical cystectomy 4-8 weeks after completion of neoadjuvant therapies.

4-8 weeks post-treatment

Follow-up

Participants are monitored for adverse events and effectiveness for up to 30 days post-cystectomy.

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

  • Cisplatin
  • Durvalumab
  • Gemcitabine
  • Nadofaragene Firadenovec

Trial Overview

The TRIFECTA trial is examining the safety and effectiveness of combining gene therapy (nadofaragene firadenovec) with chemotherapy drugs (gemcitabine, cisplatin) and an immunotherapy drug (durvalumab), compared to the current standard care before surgical removal of the bladder.

How Is the Trial Designed?

1

Treatment groups

Experimental Treatment

Group I: Treatment (durvalumab, chemotherapy, nadofaragene firadenovec)Experimental Treatment9 Interventions

Find a Clinic Near You

Who Is Running the Clinical Trial?

University of Washington

Lead Sponsor

Trials
1,858
Recruited
2,023,000+

Ferring Pharmaceuticals

Industry Sponsor

Trials
323
Recruited
1,242,000+
Pierre-Yves Berclaz profile image

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 profile image

Jean-Frédéric Paulsen

Ferring Pharmaceuticals

Chief Executive Officer since 2023

Master’s degree in Finance from the London School of Economics and Political Science

Citations

1.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/41253655/

Real-world outcomes of nadofaragene firadenovec for BCG ...

With median follow-up of 13.9 months, cystectomy-free and overall survival were 93% and 95%, respectively. Progression occurred in 5 patients.

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.

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.

The effectiveness and value of nadofaragene firadenovec, ...

In the pivotal trial of oportuzumab monatox, 36 (40%) of 89 patients with CIS ± Ta/T1 disease achieved a CR at 3 months, declining to 17% at 12 months. For ...

FINAL RESULTS FROM A PHASE 3 TRIAL

Nadofaragene firadenovec provided nearly half of participants with bladder preservation at 60 months and represents a safe intravesical treatment option.

Bladder Cancer Real-world outcomes of nadofaragene ...

Conclusions. Our multicenter data support the effectiveness and safety of nadofaragene firadenovec in patients with BCG-unresponsive NMIBC. ...

Results from a phase III trial.

Background: Patients (pts) with BCG-unresponsive NMIBC are at significant risk for disease recurrence and progression. While cystectomy can be curative, ...