Pembrolizumab Plus Y90 Radioembolization in HCC Subjects

Exclusion Criteria

• •All disease must be amenable to embolization in one or two procedures
• •Childs-Pugh Cirrhotic Status A or B with a maximum score of 7
• •No evidence of clinically apparent ascites or active encephalopathy, and/or varices that have not been treated. Subjects with controlled ascites or encephalopathy are eligible so long as they meet Childs-Pugh score criterion. Please note that controlled ascites and encephalopathy require scores of 2 each when calculating the C-P score.
• •No prior systemic therapy or radiotherapy (including Y90 radioembolization or cyberknife) for HCC. No prior TAE or TACE allowed. Previous liver resection and ablation therapy is permitted. Allowed prior therapies must be completed 4 weeks prior to the baseline scan, and untreated measurable disease (as per RECIST1.1) must be present.
• •Demonstrate adequate organ function as defined in the table below. All screening labs to be obtained within 28 days prior to registration:
• •Hematological:
• •Absolute Neutrophil Count (ANC) ≥ 1.5 x 10\^9/L; Hemoglobin (Hgb) ≥ 9 g/dL; Platelet Count ≥ 60 x 10\^9/L
• •Renal:
• •Calculated creatinine clearance ≥ 60 cc/min
• •Hepatic:
• •Bilirubin \< 2.0 X ULN; Aspartate aminotransferase (AST) ≤ 5 × ULN; Alanine aminotransferase (ALT) ≤ 5 × ULN
• •Coagulation:
• •International Normalized Ratio (INR) or Prothrombin Time (PT) Activated Partial Thromboplastin Time (aPTT) ≤1.5
• •Females of childbearing potential must have a negative serum pregnancy test within 72 hours prior to registration.
• •Females of childbearing potential and males must be willing to abstain from heterosexual activity or to use effective methods of contraception from the time of informed consent until 120 days after treatment discontinuation.
• •Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
• •As determined by the enrolling physician or protocol designee, ability of the subject to understand and comply with study procedures for the entire length of the study
• •Is willing to undergo a mandatory pre-treatment (all subjects) and post-treatment (10 subjects) research biopsy at the centers participating in research biopsies
• •Subjects meeting any of the criteria below may not participate in the study:
• •Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of study registration
• •Diagnosis of immunodeficiency or is receiving systemic steroid therapy (other than oral contraceptives) or any other form of immunosuppressive therapy within 7 days prior to registration.
• •Active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g.thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency.) is not considered a form of systemic treatment.
• •Known history of active TB
• •Hypersensitivity to pembrolizumab or any of its excipients
• •Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to registration or who has not recovered (i.e., ≤ Grade 1 or baseline) from adverse events due to agents administered \> 4 weeks prior
• •Has had prior chemotherapy, targeted small molecule therapy or radiation therapy within 2 weeks prior to registration, or who has not recovered (i.e., (i.e., ≤ Grade 1 or baseline)) from AEs due to previously administered agents
• •If had major surgery, subject must have recovered adequately from the toxicity and/or complications from the intervention prior to study registration
• •Complete portal vein occlusion
• •Vascular abnormalities or bleeding diathesis that indicates hepatic artery catheterization is contraindicated
• •Received prior therapy with an anti-PD-1, anti-PD-L1, or anti-CTLA-4 antibody
• •Known history of HIV
• •Untreated active HBV
• •Dual infection with HBV/HCV or other hepatitis combinations at study entry
• •Known history of, or any evidence of active, non-infectious pneumonitis
• •History of organ or stem cell transplantation including previous history of liver transplantation
• •Active infection requiring systemic therapy
• •Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study).
• •Has history or current evidence of any condition, therapy or laboratory abnormality that may confound results or interfere with subject's participation in the trial.
• •Known additional malignancy that is active and/or progressive requiring treatment; exceptions include basal cell or squamous cell skin cancer, in situ cervical or bladder cancer, or other cancer for which the subject has been disease-free for at least three years.
• •Has received a live vaccine within 30 days of planned start of study therapy.