This phase II trial studies how well nivolumab and ipilimumab work in treating patients with a type of genetic mutation called CDK12 loss and prostate cancer or other cancers that have spread to other places in the body. Cancer is caused by changes (mutations) to genes that control the way our cells function; especially how they repair mistakes that crop up during regular growth and turnover. The normal proof-reading system in the cells tries to fix the DNA mistakes. CDK12 is part of the body's proof-reading system that fixes mistakes in genetic information. Tumor cells that carry CDK12 loss cannot fix these mistakes well. Immunotherapy with monoclonal antibodies, such as nivolumab and ipilimumab, may help the body’s immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. The purpose of this study is to test the effectiveness (how well the drug works), safety, and tolerability of the investigational drug combination of nivolumab plus ipilimumab for metastatic prostate cancer and other cancer types that have mutations of the CDK12 gene making this gene stop working.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT03570619.
PRIMARY OBJECTIVES:
I. To determine the efficacy of checkpoint inhibitor immunotherapy with nivolumab and ipilimumab combination therapy followed by nivolumab monotherapy in patients with metastatic prostate cancer harboring loss of CDK12 function.
SECONDARY OBJECTIVES:
I. To determine the efficacy of checkpoint inhibitor immunotherapy with nivolumab and ipilimumab combination therapy followed by nivolumab monotherapy in patients with metastatic non-prostate cancer harboring loss of CDK12 function.
II. To determine the safety and tolerability of nivolumab and ipilimumab combination therapy followed by nivolumab monotherapy in patients with metastatic cancers with loss of CDK12 function.
III. To evaluate other measures of clinical efficacy of checkpoint inhibitor immunotherapy in metastatic tumors with loss of CDK12 function.
IV. To assess the quality of life (QoL) in subjects treated on protocol therapy.
EXPLORATORY OBJECTIVES:
I. To assess changes in the tumor genome with therapy.
II. To profile immune infiltration in tumor biopsies.
OUTLINE:
INDUCTION: Patients receive nivolumab intravenously (IV) over 30 minutes and ipilimumab IV over 90 minutes on day 1. Treatment repeats every 3 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity.
MAINTENANCE: Patients receive nivolumab IV over 30 minutes on day 1. Treatment repeats every 4 weeks for up to 10 cycles in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed every 3 months for 24 months.
Lead OrganizationUniversity of Michigan Rogel Cancer Center
Principal InvestigatorAjjai Shivaram Alva
