Sorafenib Tosylate and Pembrolizumab in Treating Patients With Advanced or Metastatic Liver Cancer

Inclusion Criteria:

• Participant must have histologically confirmed hepatocellular cancer (HCC) that is advanced or metastatic and have archival tissue available for PD-L1, PD-L2 testing (NOTE: if participant has had prior radiotherapy to the liver, a mandatory fresh biopsy will need to be obtained since radiotherapy could affect PD-1/PD-L1 immune status)
• Participants with measurable disease that has progressed are eligible if prior surgery or locoregional therapy occurred > 28 days prior to enrollment
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 (Karnofsky >= 60%)
• Child-Pugh class-A liver function
• Absolute neutrophil count (ANC) >= 1,500/ mcL
• Hemoglobin >= 8.5 g/dL
• Platelets >= 100,000/ mcL
• Serum total bilirubin =< 1.5 X upper limit of normal (ULN) OR direct bilirubin =< ULN for subjects with total bilirubin levels > 1.5 ULN
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 5 X ULN
• Creatinine within institutional normal limits or, clearance > 60 mL/ minute if serum creatinine is elevated above institution upper limit (UL)
• Have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria present
• Ability to swallow and retain oral medication
• Participants of child-bearing potential must agree to use adequate contraceptive methods (e.g., hormonal or barrier method of birth control; abstinence) prior to study entry; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
• Participant or legal representative must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure

Exclusion Criteria:

• Participants who have received prior sorafenib or anti-PD1 therapy for HCC
• Participants who have had radiotherapy or chemotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
• Any evidence of bleeding diathesis (patients on therapeutic warfarin or heparin will be excluded)
• Participants with a history of variceal bleed within 6 months prior to enrollment
• Known human immunodeficiency virus (HIV)-positive participants (even if on combination retrovirals, participant will be excluded
• Participants with chronic autoimmune disease
• Participants with known brain metastases should be excluded from this clinical trial
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Has known history of, or any evidence of active, non-infectious pneumonitis

• Participants with dual active hepatitis B virus (HBV) infection (hepatitis B surface antigen [HBsAg] positive [+] and /or detectable HBV deoxyribonucleic acid [DNA]) and, hepatitis C virus (HCV) infection (anti-HCV antibody [Ab] [+] and detectable HCV ribonucleic acid [RNA]) at study entry

  • Subjects with chronic infection by HCV who are treated with anti-hepatitis B therapy (successfully or treatment failure) or untreated are allowed on study; controlled (treated) hepatitis B subjects will be allowed if they meet the following criteria:

    • Antiviral therapy for HBV must be given for at least 12 weeks and HBV viral load must be less than 100 IU/mL prior to first dose of study drug; subjects on active HBV therapy with viral loads under 100 IU/ml should stay on the same therapy throughout study treatment
    • Subjects who are anti-HBc (+), negative for HBsAg, negative for anti-HBs, and have a HBV viral load under 100 IU/mL do not require HBV anti-viral prophylaxis
  • In addition, subjects with successful HCV treatment are allowed as long as there are >= 4 weeks between achieving sustained viral response (SVR) and start of study drug
• Pregnant or nursing female participants
• Unwilling or unable to follow protocol requirements
• Any condition which in the Investigator?s opinion deems the participant an unsuitable candidate to receive study drug
• Received a live vaccine within 30 days prior to start of study treatment