NCT05775471

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

Neoadjuvant Combination Pembrolizumab / Enfortumab Vedotin With Adjuvant Pembrolizumab Prior to and After Radical Nephroureterectomy for High-Risk Upper Tract Urothelial Carcinoma

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 21 (estimated)
• Sponsor: Jonsson Comprehensive Cancer Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

PRIMARY OBJECTIVES: I. To assess pathologic objective response rate (ORR; complete response \[CR; pT0\] and partial response \[PR; \< pT2\] rate) at the time of radical nephroureterectomy. II. To assess recurrence-free survival post radical nephroureterectomy. SECONDARY OBJECTIVE: I. To describe the side effect profile, tolerability, and surgical complications in patients receiving neoadjuvant pembrolizumab (pembro)/ enfortumab vedotin (EV) prior to RNU. EXPLORATORY OBJECTIVE: I. Correlative studies will evaluate the predictive potential of imaging and ureteroscopic response (visualization of tumor, biopsy, and cytology), and urinary, serum, and tissue biomarkers to pathologic response. OUTLINE: Patients receive pembrolizumab intravenously (IV) and enfortumab vedotin IV on study. Patients undergo radical nephroureterectomy and receive pembrolizumab IV on study Patients also undergo magnetic resonance urogram (MRU) imaging and undergo blood, urine and tissue sample collection throughout the study.

Conditions

• Renal Pelvis and Ureter Urothelial Carcinoma

Interventions

Type	Name	Description
PROCEDURE	Biopsy	Undergo tissue biopsy
PROCEDURE	Biospecimen Collection	Undergo blood and urine collection
DRUG	Enfortumab Vedotin	Given IV
PROCEDURE	MR Urography	Undergo MRU
PROCEDURE	Nephroureterectomy	Undergo nephroureterectomy
BIOLOGICAL	Pembrolizumab	Given IV

Timeline

• Start date: 2024-06-26
• Primary completion: 2027-12-01
• Completion: 2028-12-01
• First posted: 2023-03-20
• Last updated: 2026-02-05

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study