NCT05756569

Enfortumab Vedotin Plus Pembrolizumab for the Treatment of Locally Advanced or Metastatic Bladder Cancer of Variant Histology

Phase II Single-Arm Study of Enfortumab Vedotin (EV) Plus Pembrolizumab in the Treatment of Locally Advanced or Metastatic Bladder Cancer of Variant Histology

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 25 (estimated)
• Sponsor: Emory University · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase II trial tests how well enfortumab vedotin (EV) and pembrolizumab works in treating patients with bladder cancer of variant histology (a group of less common types of bladder cancer) that have spread to nearby tissue or lymph nodes (locally advanced) or that has spread from where it first started (primary site) to other places in the body (metastatic). Enfortumab vedotin is a monoclonal antibody, enfortumab, linked to an anticancer drug called vedotin. 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. 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. Giving enfortumab vedotin and pembrolizumab may kill more tumor cells in patients with locally advanced or metastatic bladder cancer of variant histology.

Detailed description

PRIMARY OBJECTIVE: I. To evaluate the anti-tumor activity of the combination of enfortumab vedotin (EV) plus pembrolizumab by assessing the overall response rate (ORR) as measured by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. SECONDARY OBJECTIVES: I. To evaluate the efficacy of the combination as measured by progression free survival, overall survival, and duration of response. II. To evaluate the safety as measured by incidence of adverse events assessed up to 2 years. EXPLORATORY OBJECTIVE: I. To assess tissue-based assays in archival tissue and correlative changes in peripheral T-cell subsets, myeloid derived suppressor cells (MDSC), blood inflammatory markers and cytokines. OUTLINE: Patients receive enfortumab vedotin intravenously (IV) and pembrolizumab IV on study. Patients also undergo computed tomography (CT) scan or magnetic resonance imaging (MRI), and collection of blood throughout the trial.

Conditions

• Bladder Squamous Cell Carcinoma
• Locally Advanced Bladder Carcinoma
• Malignant Renal Pelvis Neoplasm
• Malignant Ureter Neoplasm
• Malignant Urethral Neoplasm
• Metastatic Bladder Carcinoma
• Stage III Bladder Cancer AJCC v8
• Stage IV Bladder Cancer AJCC v8
• Unresectable Bladder Carcinoma
• Urachal Adenocarcinoma
• Bladder Adenocarcinoma

Interventions

Type	Name	Description
PROCEDURE	Biospecimen Collection	Undergo collection of blood
PROCEDURE	Computed Tomography	Undergo CT
DRUG	Enfortumab Vedotin	Given IV
PROCEDURE	Magnetic Resonance Imaging	Undergo MRI
BIOLOGICAL	Pembrolizumab	Given IV
OTHER	Questionnaire Administration	Ancillary studies

Timeline

• Start date: 2023-09-26
• Primary completion: 2026-12-16
• Completion: 2027-12-16
• First posted: 2023-03-06
• Last updated: 2025-07-28

Locations

4 sites across 1 country: United States

Regulatory

• FDA-regulated drug study