Ignite Creation Date:
2025-12-24 @ 9:10 PM
Ignite Modification Date:
2025-12-25 @ 7:00 PM
Study NCT ID:
NCT04953104
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2025-10-09
First Post:
2021-06-28
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
ARID1A and/or KDM6A Mutation and CXCL13 Expression
Sponsor:
M.D. Anderson Cancer Center
Organization:
Study Overview
Official Title:
A Phase II Clinical Trial to Investigate ARID1A and/or KDM6A Mutation and CXCL13 Expression in the Pre-treatment Tumor Samples as a Combinatorial Predictive Biomarker for Immune Checkpoint Therapy in Metastatic Urothelial Cancer
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2025-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This phase II trial studies the effect of nivolumab in urothelial cancer that has spread to other places in the body (metastatic), specifically in patients with aberrations in ARID1A gene (ARID1A mutation) and correlate with expression level of CXCL13, an immune cytokine. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving nivolumab may help control the disease in patients with urothelial cancer or solid tumors. This trial aims at enriching patient selection based on genomic and immunological attributes of the tumor.
Detailed 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.
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.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: