Recruiting
Phase 2

Enfortumab Vedotin & Pembrolizumab

Sponsor:

Fox Chase Cancer Center

Code:

NCT07908979

Conditions

Bladder Cancer

Urothelial Carcinoma

Muscle-Invasive Bladder Carcinoma

Muscle-invasive Bladder Urothelial Carcinoma

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Enfortumab vedotin

Pembrolizumab

Cisplatin

Gemcitabine

Fluorouracil

Study Details

Brief 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.

Conditions

Bladder Cancer

Urothelial Carcinoma

Muscle-Invasive Bladder Carcinoma

Muscle-invasive Bladder Urothelial Carcinoma

Study ID

NCT07908979

Start date

Oct 16, 2026

Status verified date

Oct, 2026

Completion date

Nov 1, 2031

Anticipated

Primary completion date

Oct 1, 2029

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • 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).
  • 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

Exclusion Criteria:

  • 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.
  • 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

Study Design

Enrollment

70 participants

Anticipated

Allocation

Non randomized

Intervention Model

Crossover

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Arm A: Neoadjuvant Enfortumab Vedotin Plus Pembrolizumab With Restaging

Participants 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.

experimental: Arm B: Additional Enfortumab Vedotin Plus Pembrolizumab for ctDNA-Positive Participants

Participants 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.

experimental: Arm C: Maintenance Pembrolizumab With Active Surveillance

Participants meeting protocol-defined criteria may undergo active surveillance while receiving maintenance pembrolizumab and scheduled disease evaluations.

experimental: Arm D: Definitive Chemoradiation

Participants requiring definitive bladder-directed treatment may receive chemoradiation with radiation therapy and investigator-selected radiosensitizing chemotherapy according to protocol specifications.

experimental: Arm E: Radical Cystectomy

Participants requiring definitive surgical management may undergo radical cystectomy.

Interventions

Enfortumab vedotin

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

Pembrolizumab

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

Cisplatin

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

Gemcitabine

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

Fluorouracil

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

Mitomycin c

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

Radical cystectomy

Surgical removal of the bladder performed according to institutional standards.

Radiation therapy

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

Primary outcome measure

  • 2-Year Metastasis-Free Survival (MFS) [ Time Frame: 2 years ]

Central Contacts and Locations

Central contacts

Investigator-Sponsored Research Unit ISRU

2678388380protocoldev@fccc.edu

Locations

Fox Chase Cancer Center - Philadelphia

Recruiting

Philadelphia, Pennsylvania, United States, 19111-2497

Contacts

Pooja Ghatalia, MD

Pooja.Ghatalia@tuhs.temple.edu

More Information

Sponsor

Fox Chase Cancer Center

Last update posted

Nov 2, 2026

Last verified

Oct, 2026

Keywords

  • Enfortumab vedotin
  • Pembrolizumab
  • Muscle-Invasive Bladder Cancer
  • MIBC
  • Bladder Cancer
  • Urothelial Carcinoma
  • ctDNA
  • Circulating Tumor DNA
  • Bladder Preservation

Trial information was received from ClinicalTrials.gov and was last updated on 2026-11-03. This information was provided to ClinicalTrials.gov by Fox Chase Cancer Center on 2026-11-02. Recruitment status is synced daily from ClinicalTrials.gov and may not reflect the sponsor's current status. Confirm during your call.