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Bladder CancerPhase 2RETAIN-3NCT07908979

Risk-Enabled Therapy After Initiating EV/Pembro for Bladder Cancer

A Phase 2 study testing Enfortumab vedotin, Pembrolizumab and Cisplatin in people with Bladder Cancer and Urothelial Carcinoma, run by Fox Chase Cancer Center at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

RETAIN-3 is a phase II study in patients with cT2-T3N0M0 muscle-invasive urothelial carcinoma of the bladder. Participants will receive neoadjuvant enfortumab vedotin and pembrolizumab followed by clinical and biomarker-based assessment to inform subsequent treatment management. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Enfortumab vedotin, Pembrolizumab and Cisplatin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
70 participants
Where
1 siteUnited States
Study dates
16 Oct 2026to 1 Nov 2031
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Primary urothelial or predominantly urothelial carcinoma of the bladder confirmed from pathology report. Patients with some component of variant histology mixed with predominant urothelial carcinoma will be allowed. Upper tract urothelial carcinoma patients are not allowed.
  • Urothelial carcinoma of the prostatic urethra in men is allowed
  • Histologic evidence of muscularis propria invasion.
  • AJCC(22) clinical stage T2-T3 N0M0.
  • No radiographic evidence of lymph node positive disease as per RECIST 1.1 (≥15 mm short axis diameter). If a lymph node is greater than 1.5 cm, it must be biopsy proven negative for the patient to be eligible.
  • No metastatic disease (M0).
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  • ECOG performance status 0, or 1.
  • Negative pregnancy test in women of child bearing potential within 72 hours of the first dose of study treatment.
  • Normal organ and bone marrow function

Who cannot join

  • Any component of small cell histology.
  • Prior systemic chemotherapy for muscle-invasive urothelial cancer of the bladder.
  • Uncontrolled diabetes (HbA1c >8.5%)
  • Pre-existing sensory or motor neuropathy grade > 2
  • Has a known additional malignancy that has had progression or has required active treatments in the last two years except for locally curable cancers that have been apparently cured. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer. Patients with intermediate or low risk prostate cancer as defined by the National Comprehensive Cancer Network (NCCN) risk stratification guidelines may be eligible for enrollment.
  • Patients who have received experimental agents within 4 weeks of study entry.
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  • Patients who have received enfortumab vedotin based treatment in the past.
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection (defined by current oral or intravenous antibiotic therapy), symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Pregnant women are excluded from this study due to the potential for teratogenic or abortifacient effects of cytotoxic therapy.
  • HIV-infected patients on effective anti-retroviral therapy with an undetectable viral load are eligible
  • Any condition requiring systemic treatment with corticosteroids (> 10 mg daily prednisone or equivalent) or other immunosuppressive medications within 7 days prior to first dose of study drug. Inhaled or topical steroids and adrenal replacement steroid doses < 10 mg daily prednisone or equivalent are permitted in the absence of active autoimmune disease. Use of steroids as pre-medication for contrast allergy prior to PET scans or CT scans is permitted.
  • History of autoimmune disease including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis. Any history of autoimmune disease not explicitly listed above should be evaluated by the Principal Investigator and may result in exclusion based on clinical judgment.
  • Prior treatment with CD137 agonists, anti-programmed death-1 (PD-1), or anti-PD-L1 therapeutic antibody or pathway-targeting agents. Has had an allogenic tissue/solid organ transplant.
  • Treatment with systemic immunostimulatory agents (including but not limited to interferons or interleukin [IL]-2) within 4 weeks or five half-lives of the drug, whichever is shorter, prior to enrolment.
  • Allergy to EV, pembrolizumab or any excipient in the products

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Investigator-Sponsored Research Unit ISRU contact

2678388380

protocoldev@fccc.edu

United States1 site, 1 recruiting

  • Fox Chase Cancer Center - Philadelphia

    Philadelphia, Pennsylvania, 19111-2497

    Pooja Ghatalia, MD, Pooja.Ghatalia@tuhs.temple.edu

    Recruiting

Other trials in United States

About this study

Official title: GU-254: A Phase II Trial of Risk-Enabled Therapy After Initiating Neoadjuvant Enfortumab Vedotin/Pembrolizumab for Bladder Cancer (RETAIN-3)

RETAIN-3 is a phase II study in patients with cT2-T3N0M0 muscle-invasive urothelial carcinoma of the bladder. Participants will receive neoadjuvant enfortumab vedotin and pembrolizumab followed by clinical and biomarker-based assessment to inform subsequent treatment management.

Read the detailed description

RETAIN-3 is a multicenter, open-label, phase II study evaluating a biomarker- and response-adapted bladder preservation strategy in patients with cT2-T3N0M0 muscle-invasive bladder cancer treated with neoadjuvant enfortumab vedotin and pembrolizumab. Following treatment, participants undergo clinical restaging and biomarker assessment to guide subsequent management, which may include active surveillance, maintenance therapy, cystectomy, or chemoradiation. The study aims to determine whether a biomarker-guided approach can preserve the bladder in selected patients while maintaining favorable oncologic outcomes.

Being tested
Enfortumab vedotin, Pembrolizumab, Cisplatin, Gemcitabine, Fluorouracil
Keywords
Enfortumab vedotin, Pembrolizumab, Muscle-Invasive Bladder Cancer, MIBC, Bladder Cancer, Urothelial Carcinoma, ctDNA, Circulating Tumor DNA, Bladder Preservation
Medical subject headings
Urinary Bladder Neoplasms, Carcinoma, Transitional Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Enfortumab vedotinDrug

    1.25 mg/kg (maximum 125 mg) intravenously on Days 1 and 8 of each 21-day cycle for 3 cycles.

  • PembrolizumabDrug

    200 mg intravenously on Day 1 of each 21-day cycle or subcutaneous pembrolizumab/berahyaluronidase formulation administered per protocol.

  • CisplatinDrug

    Cisplatin administered as a radiosensitizing chemotherapy regimen in participants receiving chemoradiation.

  • GemcitabineDrug

    Gemcitabine administered as a radiosensitizing chemotherapy regimen in participants receiving chemoradiation.

  • FluorouracilDrug

    Fluorouracil administered as a radiosensitizing chemotherapy regimen in participants receiving chemoradiation.

  • Mitomycin cDrug

    Mitomycin C administered in combination with fluorouracil as a radiosensitizing chemotherapy regimen in participants receiving chemoradiation.

  • Radical cystectomyProcedure or surgery

    Surgical removal of the bladder performed according to institutional standards.

  • Radiation therapyProcedure or surgery

    Definitive bladder-preserving treatment consisting of external beam radiation therapy administered with concurrent radiosensitizing chemotherapy according to institutional standards and protocol specifications.

Study groups in NCT07908979
Study groupRoleWhat they receive
Arm A: Neoadjuvant Enfortumab Vedotin Plus Pembrolizumab With RestagingExperimentalParticipants receive neoadjuvant enfortumab vedotin plus pembrolizumab for 3 cycles followed by protocol-specified clinical restaging and biomarker assessment. All enrolled participants begin study treatment in this arm.
Receives: Drug: Enfortumab vedotin; Drug: Pembrolizumab
Arm B: Additional Enfortumab Vedotin Plus Pembrolizumab for ctDNA-Positive ParticipantsExperimentalParticipants with positive post-treatment circulating tumor DNA (ctDNA) and favorable clinical restaging findings may receive an additional 3 cycles of enfortumab vedotin plus pembrolizumab followed by repeat assessment.
Receives: Drug: Enfortumab vedotin; Drug: Pembrolizumab
Arm C: Maintenance Pembrolizumab With Active SurveillanceExperimentalParticipants meeting protocol-defined criteria may undergo active surveillance while receiving maintenance pembrolizumab and scheduled disease evaluations.
Receives: Drug: Pembrolizumab
Arm D: Definitive ChemoradiationExperimentalParticipants requiring definitive bladder-directed treatment may receive chemoradiation with radiation therapy and investigator-selected radiosensitizing chemotherapy according to protocol specifications.
Receives: Drug: Cisplatin; Drug: Gemcitabine; Drug: Fluorouracil; Drug: Mitomycin c; Procedure: Radiation therapy
Arm E: Radical CystectomyExperimentalParticipants requiring definitive surgical management may undergo radical cystectomy.
Receives: Procedure: Radical cystectomy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 2-Year Metastasis-Free Survival (MFS)

    Metastasis-free survival is defined as the time from initiation of neoadjuvant therapy to metastatic urothelial carcinoma or death from any cause, whichever occurs first.

    Measured: 2 years

Secondary outcomes (8)

  1. Bladder-intact metastasis-free survival in active surveillance patients

    Measured: 2 years

  2. Pathologic complete response (pT0) rate among participants undergoing cystectomy

    Measured: At cystectomy

  3. Clinical complete response rate

    Measured: Up to 5 years

  4. Rate of urothelial carcinoma recurrence in active surveillance participants

    Measured: Up to 5 years

  5. Overall survival (OS)

    Measured: Up to 5 years

  6. Rate of distant recurrence among post-treatment ctDNA-positive participants undergoing definitive local therapy

    Measured: Up to 5 years

  7. Proportion of participants undergoing cystectomy

    Measured: Up to 5 years

  8. Bladder-intact metastasis-free survival in all evaluable participants

    Measured: 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Nov 2026
  2. Study start16 Oct 2026
  3. Primary completion1 Oct 2029 (estimated)
  4. Study completion1 Nov 2031 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Crossover
Model description
All participants receive neoadjuvant enfortumab vedotin and pembrolizumab followed by response- and biomarker-guided treatment management.
Masking
None (open label)
Enrolment
70 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07908979
Sponsor's protocol ID
26-1030
Other IDs
GU-254
Acronym
RETAIN-3
Status last verified
Oct 2026
First submitted
19 Oct 2026
Last updated
2 Nov 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Enfortumab vedotin, Pembrolizumab and Cisplatin in people with Bladder Cancer and Urothelial Carcinoma, run by Fox Chase Cancer Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 2 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Investigator-Sponsored Research Unit ISRU (2678388380, protocoldev@fccc.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

2-Year Metastasis-Free Survival (MFS) (time frame: 2 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07908979.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Nov 2026.

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