TRIFECTANCT07332351

Neoadjuvant Intravesical Nadofaragene Firadenovec With Enfortumab Vedotin and Pembrolizumab for the Treatment of Muscle Invasive Bladder Cancer, TRIFECTA Trial

StatusNot Yet Recruiting

PhasePhase 2

SponsorUniversity of Washington

Primary completionJun 1, 2027 (estimated)

At risk: Primary completion moved 5 months later, primary endpoint(s) modified, and 1 more.

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Record History

All 6 versions: 5 with changes below, 1 re-verified with no change. See every version on ClinicalTrials.gov ↗

Notable Nov 9, 2026 Primary endpoint(s) modified Show 8 more changesShow less
- Eligibility criteria expanded, about 22 words
- Primary completion pushed from Jan 1, 2027 to Jun 1, 2027
- Enrollment reduced: 33 → 24 participants
- Study completion pushed from Feb 1, 2027 to Jul 1, 2027
- Interventions modified
- Secondary endpoints: 3 to 4
- Study description shortened, about 16 words
- Study title revised
Notable Sep 15, 2026 Start date: Sep 1, 2026 to Dec 1, 2026
- Eligibility criteria expanded, about 23 words
- Secondary endpoints: details revised at 1 of 3 entries
- Site details revised
Notable Jun 4, 2026 Start date: Jun 1, 2026 to Sep 1, 2026v3
Notable Mar 11, 2026 Start date: Mar 1, 2026 to Jun 1, 2026v2
Jan 8, 2026 Study First Submitted

Notable: the plan changed

Endpoints

Primary

Proportion of patients who receive nadofaragene firadenovec and complete at least 2 cycles of enfortumab vedotin and pembrolizumab in the neoadjuvant period followed by radical cystectomy

Timeframe: Within 10 weeks from last neoadjuvant therapy dose

Secondary (4)

Incidence of grade 3 or higher treatment-related adverse events (AE)

Incidence of AEs

Pathologic complete response (pCR) on radical cystectomy (RC) specimen

Downstaging (≤ ypT1N0) on RC specimen

Arms and interventions

TreatmentExperimental

Patients receive standard of care neoadjuvant therapies for muscle invasive bladder cancer including: enfortumab vedotin IV on days 1 and 8 and pembrolizumab IV on day 1 of each cycle. In addition, patients also receive nadofaragene firadenovec intravesically on day 1 of cycle 1 (total of 1 dose in neoadjuvant period). Cycles repeat every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Starting 4-8 weeks after treatment, patients undergo RC per standard clinical care. Additionally, patients undergo urine and blood sample collection and CT, MRI or PET/CT throughout the study.

Biologicals: Nadofaragene Firadenovec, Pembrolizumab

Drugs: Enfortumab Vedotin

Procedures: Radical Cystectomy, Biospecimen Collection, Computed Tomography, Positron Emission Tomography, Magnetic Resonance Imaging

Sites

1 site in 1 country

Fred Hutch/University of Washington Cancer ConsortiumSeattle, Washington, United States

About this trial

This phase II trial tests the effect of intravesical nadofaragene firadenovec in combination with enfortumab vedotin and pembrolizumab before (neoadjuvant) radical cystectomy in treating patients with muscle invasive bladder cancer. The combination of enfortumab vedotin and pembrolizumab are already considered standard of care in the treatment of muscle invasive bladder cancer. This trial attempts to determine whether the addition of nadofaragene firadenovec to the current standard regiment is safe and can improve oncological outcomes for those with muscle invasive bladder cancer. Nadofaragene firadenovec, a type of intravesical gene therapy, is a weakened adenovirus that carries a copy of the gene for interferon alfa-2b. This medication gets absorbed by the bladder and stimulates the bladder to naturally create interferon alfa-2b, which is thought to kill bladder cancer. Nadofaragene firadenovec is given in a solution that is placed directly into the bladder (intravesical) using a thin tube called a catheter. It is a medication that is already Food and Drug Administration approved for the treatment of non-muscle invasive bladder cancer. Enfortumab vedotin is a monoclonal antibody, enfortumab, linked to an anticancer drug called vedotin. It works by helping the immune system to slow or stop the growth of tumor cells. Enfortumab attaches to a protein called nectin-4 on tumor cells in a targeted way and delivers vedotin to kill them. It is a type of antibody-drug conjugate. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the tumor, and may interfere with the ability of tumor cells to grow and spread. Investigators aim to assess whether adding intravesical nadofaragene firadenovec to the current recommended treatment of enfortumab vedotin and pembrolizumab before undergoing a radical cystectomy may be safe, tolerable, and/or effective in treating patients with muscle-invasive bladder cancer.

Trial details

Enrollment: 24 participants (estimated)
Started: Dec 1, 2026
Study completion: Jul 1, 2027 (estimated)
Eligibility: 18 and older, all sexes, no healthy volunteers
Design: Interventional, open label, treatment
Oversight: Data monitoring committee, FDA-regulated drug
Conditions: Urinary Bladder Neoplasms, Muscle Invasive Bladder Urothelial Carcinoma, Stage II Bladder Cancer AJCC v8, Stage IIIA Bladder Cancer AJCC v8
Collaborators: Ferring Pharmaceuticals
Official title: Intravesical Nadofaragene Firadenovec With Enfortumab Vedotin and Pembrolizumab in Patients With Muscle Invasive Bladder Cancer (TRIFECTA)
First posted: Jan 12, 2026
Registry updated: Nov 13, 2026
Last verified: Nov 2026

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