NCT07217496

N-803 in Combination With Pembrolizumab and Enfortumab Vedotin for Treatment of Urothelial Cancer

Phase Ib Trial Combining N-803 and Pembrolizumab With Shorter Duration of Enfortumab Vedotin in Treatment-Naïve Patients With Metastatic Urothelial Carcinoma

• Status: Withdrawn
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: Vadim S Koshkin · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase Ib trial will investigate the effect of N-803 in combination with pembrolizumab and enfortumab vedotin in treating participants with urothelial cancer 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).

Detailed description

PRIMARY OBJECTIVE: I. To assess the safety and tolerability of the treatment regimen (N-803, enfortumab vedotin, and pembrolizumab). II. To assess 12-month progression-free survival (PFS) of participants with locally advanced or metastatic urothelial carcinoma (mUC) receiving enfortumab vedotin (EV) plus pembrolizumab and N-803. SECONDARY OBJECTIVE: I. To evaluate the preliminary efficacy of the treatment regimen (EV, pembrolizumab, and N-803) as measured by complete response rate (CRR), objective response rate (ORR), clinical benefit rate (CBR), 12-month overall survival (12-OS), median duration of response (mDOR), median progression-free survival (mPFS) and median overall survival (mOS). EXPLORATORY OBJECTIVES: I. To determine the immune status of the tumor microenvironment using multiplex immunohistochemistry (IHC) and identify potential correlations with participant outcomes. II. To determine T-cell receptor (TCR) clonality. III. To analyze tumor/immune gene expression profiles, DNA methylation, DNA damage response and repair (DDR) genes \[e.g., BRCA1/2, ERCC1/2\]). IV. Observe changes in circulating tumor DNA (ctDNA). V. To monitor the maintenance of absolute lymphocyte counts (ALC) relative to baseline, throughout the course of treatment. OUTLINE: This is an open-label, single center, phase Ib single-arm trial with a safety lead-in cohort. Participants will receive treatment for up to 12 cycles administered. Depending on response, participants may continue treatment with pembrolizumab and N-803 for maximum of 2 years. Participants will undergo safety follow-up approximately 30 days following the end of study treatment and be followed for survival until death (any cause) or end of study for a up to 5 years from start of treatment.

Conditions

• Metastatic Urothelial Carcinoma
• Urothelial Carcinoma
• Locally Advanced Urothelial Carcinoma
• Urothelial Cancer

Interventions

Type	Name	Description
DRUG	Nogapendekin Alfa Inbakicept (N803)	Given subcutaneously (SC)
DRUG	Enfortumab Vedotin (EV)	Given intravenously (IV)
DRUG	Pembrolizumab	Given intravenously (IV)
PROCEDURE	Research Biospecimen Collection	Undergo blood collection for research purposes
PROCEDURE	Radiographic Imaging	Undergo radiographic imaging for disease assessment
PROCEDURE	Tumor Biopsy	Undergo tumor biopsy

Timeline

• Start date: 2026-02-15
• Primary completion: 2027-05-30
• Completion: 2027-05-30
• First posted: 2025-10-16
• Last updated: 2026-03-17

Regulatory

• FDA-regulated drug study