Enfortumab Vedotin, Pembrolizumab and Quemliclustat for the Treatment of Unresectable Locally Advanced and Metastatic Urothelial Cancer

Summary

This phase Ib/II trial tests the safety, side effects, and best dose of quemliclustat in combination with enfortumab vedotin and pembrolizumab, and to see how well the combination works for the treatment of bladder, renal pelvis, or ureter urothelial cancer that cannot be removed by surgery (unresectable), that has 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. 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. 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. Quemliclustat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving quemliclustat in combination with enfortumab vedotin and pembrolizumab and may be safe, tolerable and/or effective in treating patients with unresectable locally advanced and metastatic urothelial cancer.

Conditions

• Locally Advanced Bladder Urothelial Carcinoma
• Locally Advanced Renal Pelvis Urothelial Carcinoma
• Locally Advanced Ureter Urothelial Carcinoma
• Metastatic Bladder Giant Cell Urothelial Carcinoma
• Metastatic Renal Pelvis Urothelial Carcinoma
• Metastatic Ureter Urothelial Carcinoma
• Stage IIIB Bladder Cancer AJCC v8
• Stage IV Bladder Cancer AJCC v8
• Stage IV Renal Pelvis Cancer AJCC v8
• Stage IV Ureter Cancer AJCC v8
• Unresectable Bladder Urothelial Carcinoma
• Unresectable Renal Pelvis Urothelial Carcinoma
• Unresectable Ureter Urothelial Carcinoma

Interventions

DRUG

Quemliclustat

Given IV

PROCEDURE

Biospecimen Collection

Undergo blood sample collection

PROCEDURE

Computed Tomography

Undergo CT scan

DRUG

Enfortumab Vedotin

Given IV

PROCEDURE

Magnetic Resonance Imaging

Undergo MRI

BIOLOGICAL

Pembrolizumab

Given IV

PROCEDURE

Biopsy Procedure

Undergo tumor biopsy

Sponsors & Collaborators

• Bench to Bedside (B2B)

  collaborator UNKNOWN

• Arcus Biosciences, Inc.

  collaborator INDUSTRY

• Fred Hutchinson Cancer Center

  lead OTHER

Principal Investigators

• Rosa Nadal Rios, MD, PhD · Fred Hutch/University of Washington Cancer Consortium

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2026-12-01

Primary Completion

2029-07-16

Completion

2029-07-16

FDA Drug

Yes

Countries

• United States

Study Locations