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

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.