Actively Recruiting

Phase 2
Age: 18Years +
All Genders
NCT05775471

Pembrolizumab and Enfortumab Vedotin With Pembrolizumab Prior to and After Radical Nephroureterectomy for High-Risk Upper Tract Urothelial Cancer

Led by Jonsson Comprehensive Cancer Center · Updated on 2026-02-05

21

Participants Needed

1

Research Sites

231 weeks

Total Duration

On this page

Sponsors

J

Jonsson Comprehensive Cancer Center

Lead Sponsor

M

Merck Sharp & Dohme LLC

Collaborating Sponsor

AI-Summary

What this Trial Is About

This phase II clinical trial tests how well pembrolizumab plus enfortumab vedotin prior to and after radical nephroureterectomy works in treating patients with high-risk upper tract urothelial cancer. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Enfortumab vedotin (EV) 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 cancer cells. Enfortumab attaches to a protein called nectin-4 on cancer cells in a targeted way and delivers vedotin to kill them. It is a type of antibody-drug conjugate. Radical nephroureterectomy (RNU) is the surgical removal of a kidney and its ureter. Giving pembrolizumab plus enfortumab vedotin before surgery may make the tumor smaller and may reduce the amount of normal tissue that needs to be removed and giving pembrolizumab after surgery may kill any remaining cancer cells.

CONDITIONS

Official Title

Pembrolizumab and Enfortumab Vedotin With Pembrolizumab Prior to and After Radical Nephroureterectomy for High-Risk Upper Tract Urothelial Cancer

Who Can Participate

Age: 18Years +
All Genders

Eligibility Criteria

Eligible

You may qualify if you...

  • Male or female participants at least 18 years old with confirmed high-risk upper tract urothelial carcinoma
  • Male participants must agree to use contraception during treatment and for 6 months after last dose and avoid donating sperm during this time
  • Female participants must not be pregnant or breastfeeding and either not be women of childbearing potential or agree to use contraception during treatment and for 6 months after last dose
  • Provide archival tumor tissue or newly obtained tumor biopsy not previously irradiated
  • Have Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 evaluated within 7 days before first treatment
  • Absolute neutrophil count (ANC) ≥ 1500/uL within 10 days before treatment start
  • Platelets ≥ 100,000/uL within 10 days before treatment start
  • Hemoglobin ≥ 9.0 g/dL within 10 days before treatment start
  • Creatinine ≤ 1.5 times upper limit of normal or creatinine clearance ≥ 30 mL/min within 10 days before treatment start
  • Total bilirubin ≤ 1.5 times upper limit of normal or direct bilirubin ≤ upper limit of normal within 10 days before treatment start
  • AST and ALT ≤ 2.5 times upper limit of normal (or ≤ 5 times for liver metastases) within 10 days before treatment start
  • INR or PT/aPTT ≤ 1.5 times upper limit of normal unless on anticoagulants with therapeutic levels within 10 days before treatment start
Not Eligible

You will not qualify if you...

  • Women of childbearing potential with positive pregnancy test within 72 hours before allocation
  • Prior therapy with anti-PD-1, anti-PD-L1, anti-PD-L2, or other T-cell receptor agents
  • Systemic anti-cancer therapy or investigational agents within 4 weeks before allocation unless recovered from adverse effects
  • Prior radiotherapy within 2 weeks of study start unless recovered from toxicities
  • Live vaccine within 30 days before first dose
  • Participation in another investigational study or use of investigational device within 4 weeks prior
  • Diagnosis of immunodeficiency or use of systemic immunosuppressive therapy within 7 days before first dose
  • Active progressing malignancy requiring treatment within past 2 years except certain skin or carcinoma in situ
  • Active CNS metastases or carcinomatous meningitis unless stable and off steroids
  • Severe hypersensitivity to pembrolizumab or its excipients
  • Active autoimmune disease requiring systemic treatment in past 2 years
  • History or current pneumonitis requiring steroids
  • Active infection requiring systemic therapy
  • Known HIV infection unless stable on therapy with low viral load and adequate CD4 count
  • Known active hepatitis B or C infection unless treated and stable
  • Conditions or therapies interfering with study participation or safety per investigator
  • Psychiatric or substance abuse disorders interfering with trial compliance
  • Pregnant, breastfeeding, or expecting to conceive/father children through 120 days after last dose
  • History of allogenic tissue or solid organ transplant
  • Prior treatment with enfortumab vedotin or MMAE-based antibody-drug conjugates
  • Life expectancy less than 12 weeks
  • Severe hypersensitivity to any excipients in enfortumab vedotin or pembrolizumab formulations
  • Active keratitis or corneal ulcerations; superficial punctate keratitis allowed if adequately treated

AI-Screening

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Trial Site Locations

Total: 1 location

1

UCLA / Jonsson Comprehensive Cancer Center

Los Angeles, California, United States, 90095

Actively Recruiting

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Research Team

A

Ankush Sachdeva

CONTACT

How is the study designed?

Study Type

INTERVENTIONAL

Masking

NONE

Allocation

NA

Model

SINGLE_GROUP

Primary Purpose

TREATMENT

Number of Arms

1

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