Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Carcinoma

Carcinoma, Squamous Cell

Adenocarcinoma

Urinary Bladder Neoplasms

Ureteral Neoplasms

Pelvic Neoplasms

Urethral Neoplasms

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

Urethral Diseases

Ureteral Diseases

Urachal Adenocarcinoma

All Drugs and Chemicals

Antineoplastic Agents

Antibodies

Antibodies, Monoclonal

Pembrolizumab

Immunoglobulins

Immunoconjugates

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Immunologic Factors

Patients receive enfortumab vedotin IV and pembrolizumab IV on study. Patients also undergo CT scan or MRI, and collection of blood throughout the trial.

Biospecimen Collection

Computed Tomography

Enfortumab Vedotin

Magnetic Resonance Imaging

Questionnaire Administration

Bassel Nazha, MD, MPH

Wilena Session

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.

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.

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

Will be measured by Response Evaluation Criteria in Solid Tumors version 1.1, and estimated by the Clopper-Pearson method with 95% confidence intervals.

Kalan-Meier method will be used to estimate median event time and 2-year survival rate with 95% confidence interval.

Determined by occurrence of complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1.

Graded according to the Common Terminology Criteria for Adverse Events version 5.0, and will be tabulated using descriptive statistics (mean, median, minimum, maximum, standard deviation).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Enfortumab Vedotin Plus Pembrolizumab for the Treatment of Locally Advanced or Metastatic Bladder Cancer of Variant Histology	NCT05756569	Bladder Squamou... Locally Advance... Malignant Renal... Malignant Urete... Malignant Ureth... Metastatic Blad... Stage III Bladd... Stage IV Bladde... Unresectable Bl... Urachal Adenoca... Bladder Adenoca...	Biospecimen Col... Computed Tomogr... Enfortumab Vedo... Magnetic Resona... Pembrolizumab Questionnaire A...	18 Years -	Emory University
Enfortumab Vedotin Plus Pembrolizumab for the Treatment of Locally Advanced or Metastatic Bladder Cancer of Variant Histology	NCT05756569	Bladder Squamou... Locally Advance... Malignant Renal... Malignant Urete... Malignant Ureth... Metastatic Blad... Stage III Bladd... Stage IV Bladde... Unresectable Bl... Urachal Adenoca... Bladder Adenoca...	Biospecimen Col... Computed Tomogr... Enfortumab Vedo... Magnetic Resona... Pembrolizumab Questionnaire A...	18 Years -	Emory University

Spots Global Cancer Trial Database for malignant urethral neoplasm