Biomarker-Driven Therapy With Nivolumab and Ipilimumab in Treating Patients With Metastatic Hormone-Resistant Prostate Cancer Expressing AR-V7

Inclusion Criteria

• Histologically or cytologically confirmed adenocarcinoma of the prostate
• Metastatic disease as defined by two or more bone metastases confirmed by bone scintigraphy or radiographic soft tissue metastasis
• Detectable circulating tumor cells (CTCs) with detectable AR-V7 splice-variant by reverse transcriptase (RT)-polymerase chain reaction (PCR)

For second cohort (amendment 1):

The most recent therapy must be enzalutamide and enzalutamide will be continued for study duration despite progressive disease. The minimum required dose of Enzalutamide at enrolment should be no less than 80 mg once daily.

• Known castration-resistant disease, defined according to Prostate Cancer Working Group 2 (PCWG2) criteria as:
• Castrate serum testosterone level: = = 2 ng/mL OR
• Documented bone lesions by the appearance of two or more new lesions by bone scintigraphy OR
• Bidimensionally-measureable soft tissue metastatic lesion assessed by computed tomography (CT) or magnetic resonance imaging (MRI)
• Karnofsky performance status (KPS): >= 70% within 14 days before start of study treatment (Eastern Cooperative Oncology Group [ECOG] = = 2000/uL
• Neutrophils >= 1500/uL
• Platelets >= 100 x10^3/uL
• Hemoglobin > 9.0 g/dL
• Serum creatinine = = 40 mL/min (if using the Cockcroft-Gault formula)
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) = = Common Terminology Criteria for Adverse Events [CTCAE] grade 3)
• Patients are excluded if they have active brain metastases or leptomeningeal metastases; subjects with brain metastases are eligible if metastases have been treated and there is no magnetic resonance imaging (MRI) evidence of progression for at least 4 weeks after treatment is complete and within 28 days prior to the first dose of nivolumab administration; there must also be no requirement for immunosuppressive doses of systemic corticosteroids (> 10 mg/day prednisone equivalents) for at least 2 weeks prior to study drug administration
• Patients should be excluded if they have an active, known or suspected autoimmune disease (e.g. inflammatory bowel disease, rheumatoid arthritis, autoimmune hepatitis, lupus, celiac disease); subjects are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger
• Patients should be excluded if they have a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration; inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease
• Permitted therapies include topical, ocular, intra-articular, intranasal, and inhalational corticosteroids (with minimal systemic absorption); physiologic replacement doses of systemic corticosteroids are permitted, even if > 10 mg/day prednisone equivalents; a brief course of corticosteroids for prophylaxis (eg, contrast dye allergy) or for treatment of nonautoimmune conditions (e.g. delayed-type hypersensitivity reaction caused by contact allergen) is permitted
• Drugs with a predisposition to hepatoxicity should be used with caution in patients treated with nivolumab-containing regimen
• Patients should be excluded if they have a positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection
• Patients should be excluded if they have known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
• Allergies and adverse drug reaction
• History of allergy to study drug components
• History of severe hypersensitivity reaction to any monoclonal antibody
• Other pr