Nivolumab for the Treatment of Patients With Metastatic Urothelial Cancer With ARID1A Mutation and Stratify Response Based on CXCL13 Expression

Description

PRIMARY OBJECTIVE:

I. To estimate objective response rate (ORR) and overall survival (OS) in participants with ARID1A and/or KDM6A mutations receiving nivolumab and relatlimab combination therapy. II. To estimate objective response rate (ORR) and overall survival (OS) in participants with ARID1A and/or KDM6A mutations plus CXCL13-high expression and ARID1A and/or KDM6A mutations plus CXCL13-low expression, receiving nivolumab and relatlimab therapy.

SECONDARY OBJECTIVES:

I. To estimate progression free survival (PFS) in subjects with harboring ARID1A and/or KDM6A mutation treated with nivolumab and relatlimab combination therapy.

II. To estimate progression free survival (PFS) in subjects with ARID1A and/or KDM6A mutations plus CXCL13-high expression and ARID1A and/or KDM6A mutations plus CXCL13-low expression, treated with nivolumab and relatlimab combination therapy.

III. To assess peripheral and tumor infiltrating immune cell sub-populations in patients with ARID1A mutations, KDM6A mutations, ARID1A plus CXCL13-high and ARID1A plus CXCL13-low expression, KDM6A plus CXCL13-high and KDM6A plus CXCL13-low expression, to determine predictors of response and resistance.

IV. To determine the expression pattern of CXCL13 in ARID1A and/or KDM6A mutant tumors

OUTLINE:

Patients receive nivolumab intravenously (IV) over 30 minutes on day 1. Cycles repeats 28 days (4 weeks) for up to 2 years in the absence of disease or unacceptable toxicity.

After the completion of study treatment, patients are followed up for 100 days, then every 3-6 months thereafter.