Inclusion Criteria
Histological or cytological evidence of renal cell carcinoma (initial diagnosis).
Metastatic disease
Progressive disease on nivolumab + ipilimumab regimen
Measurable disease
Prior cancer treatment (excluding nivo/ipi) must be completed at least 28 days prior to registration
Demonstrate adequate organ function
Women of childbearing potential (WOCBP) must have a negative serum pregnancy test during screening and a negative urine pregnancy test within 3 days prior to first dose of study drug. If the screening serum test is done within 3 days prior to receiving the first dose of study drug, a urine test is not required.
Women of childbearing potential must be willing to abstain from heterosexual activity or to use an effective method of contraception from the time of informed consent until 5 months after the last dose of study drug.
Men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year. Men receiving study drugs and who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 7 months after the last dose of study drug.
As determined by the enrolling physician or protocol designee, ability of the patient to understand and comply with study procedures for the entire length of the study.
Life expectancy of at least 6 months per investigator discretion.
Exclusion Criteria
History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the patient?s participation for the full duration of the study, or is not in the best interest of the patient to participate, in the opinion of the treating investigator, including, but not limited to:
Myocardial infarction or arterial thromboembolic events within 6 months prior to screening or severe or unstable angina
Uncontrolled hypertension or diabetes mellitus
Another known malignancy that is progressing or requires active treatment
Any prior history of other cancer within the prior 5 years with the exception of adequately treated basal cell carcinoma or cervical intraepithelial neoplasia [CIN]/cervical carcinoma in situ or melanoma in situ)
Active infection requiring systemic therapy
Known active central nervous system (CNS) metastases and/or carcinomatous meningitis
Pregnant or breastfeeding
Any contraindication to oral agents or significant nausea and vomiting, malabsorption, or significant small bowel resection that, in the opinion of the investigator, would preclude adequate absorption
Allergy to benzamide or inactive components of entinostat
Hypersensitivity to nivolumab, ipilimumab, or any of their excipients
Treatment with any investigational drug or device within 4 weeks prior to registration
Treatment with systemic steroids within 4 weeks prior to registration
Evidence of active autoimmune disease requiring systemic treatment within the past 90 days or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents
Interstitial lung disease or history of pneumonitis requiring treatment with corticosteroids
Diagnosis of immunodeficiency; or is receiving chronic systemic corticosteroid therapy or other immunosuppressive therapy (excludes inhaled corticosteroids) within 4 weeks prior to registration
Known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)
Known active hepatitis B or hepatitis C
Has received a live vaccine within 30 days prior to planned start of study therapy