Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Carcinoma

Urinary Bladder Neoplasms

Carcinoma, Transitional Cell

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Urinary Bladder Diseases

Urologic Diseases

Male Urogenital Diseases

Transitional Cell Carcinoma

Antineoplastic Agents

All Drugs and Chemicals

Pembrolizumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

The study population will include male and female patients over the age of 18 with high grade UTUC (cN0/xM0) and is ineligible for or refuses definitive radical nephroureterectomy (RNU).

Enfortumab vedotin will be administered on Days 1 and 8 at 1.25mg/kg of every 3-week cycle by intravenous (IV) infusion given over approximately 30 minutes. Pembrolizumab will be administered on Day 1 at 200mg of every 3-week cycle by IV infusion over approximately 30 minutes. Enfortumab vedotin and Pembrolizumab may be administered for up to total of 35 cycles (approximately 2 years).

Enfortumab vedotin 1.25mg/kg on Days 1 and 8 every 3 weeks for up to 35 weeks (each cycle = 21 days)

Enfortumab vedotin

Pembrolizumab 200mg on Day 1 every 3 weeks for up to 35 weeks (each cycle = 21 days)

Tanya O'Neal, RN

Carol Goldener, RN

Jean Hoffman-Censits, MD

Jean Hoffman-Censtis, MD

This trial will evaluate the use of combination pembrolizumab and enfortumab vedotin for patients with high grade non-metastatic (cN0/NxMx, no measurable regional lymph nodes, no metastases) upper tract urothelial cancer (UTUC), preferring to forego standard of care radical nephroureterectomy (RNU) surgery. Currently these patients would not be suitable candidates for neoadjuvant trials, as the patients intention is to forego surgery. The patients are also not candidates for metastatic trials, as the patients have no measurable metastasis. The Investigators hypothesize the combination of pembrolizumab and enfortumab vedotin for patients with high grade cN0/NxMx UTUC deferring RNU will lead to event free survival outcomes similar to that achieved by RNU in a historic dataset.

This single arm phase II trial will evaluate the use of enfortumab vedotin and pembrolozumab for high grade upper tract urothelial cancer patients who are unable or unwilling to undergo standard of care nephroureterectomy.

Enfortumab vedotin IV 1.25 mg/kg days 1,8 and pembrolizumab 200 mg IV will be delivered every 21 days in 20 patients with high grade UTUC cT2-T4N0 (non-metastatic) until disease progression outside of the renal/ureter unit and/or intolerance.

Primary objective is event free survival (EFS), defined as the time to systemic relapse or death. The hypothesis is that the combination of pembrolizumab and enfortumab vedotin for patients with high grade non-metastatic UTUC deferring nephroureterectomy will lead to EFS outcomes similar to that achieved by RNU in historical dataset from the Brady Urologic Institute database (based on a subset of 85 patients with high grade UTUC cT2-T4N0 who underwent surgery without perioperative chemotherapy).

Renal Retention in High Grade Upper Tract Urothelial Cancer

Renal Retention in High Grade Upper Tract Urothelial Cancer: A Phase II Trial of Enfortumab Vedotin and Pembrolizumab in Patients With Upper Tract Urothelial Cancer (UTUC) Who Are Not Candidates for, or Refuse, Nephroureterectomy

Number of participants experiencing dose limiting toxicities and treatment-related adverse events, as defined by Common Terminology Criteria for Adverse Events Version 5.0 (CTCAE v5.0).

Number of participants without disease recurrence

Number of participants alive end of trial.

Number participants with tumor available for DNA sequencing including, FGFR mutation / fusion status, from UTUC biopsy specimens

Number of participants with immune biomarker data available from UTUC biopsy specimens

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Renal Retention in High Grade Upper Tract Urothelial Cancer	NCT05656235	High Grade Urot... Bladder Cancer Urothelial Carc...	Enfortumab vedo... Pembrolizumab	18 Years -	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Renal Retention in High Grade Upper Tract Urothelial Cancer	NCT05656235	High Grade Urot... Bladder Cancer Urothelial Carc...	Enfortumab vedo... Pembrolizumab	18 Years -	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Spots Global Cancer Trial Database for high grade urothelial carcinoma