Nivolumab and Bevacizumab in Treating Patients with Unresectable or Metastatic Liver Cancer

Inclusion Criteria

• Confirmed unresectable or metastatic hepatocellular carcinoma; confirmation either by histologic confirmation or accepted radiographic criteria
• Received at least one line of therapy with a tyrosine kinase inhibitor (TKI) (including, but not limited to sorafenib, lenvatinib, and/or regorafenib) with evidence of disease progression clinically or radiographically as deemed by investigator, or refused therapy with a TKI; no more than two lines of prior therapy are allowed
• Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST)1.1
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
• Life expectancy >= 12 weeks
• Childs Pugh A (5-6 points)
• Absolute neutrophil count (ANC) >= 1.5 k/uL
• Platelets (PLT) >= 100 k/uL
• Hemoglobin (Hb) >= 9 g/dL
• Creatinine < 2 x upper limit of normal (ULN)
• Able to provide informed consent and willing to sign an approved consent form that conforms to federal and institutional guidelines

Exclusion Criteria

• Prior treatment with anti-PD1 or anti-PD-L1 antibody therapy
• Subjects with a prior history of deep vein thrombosis (DVT)/pulmonary embolism (PE) who have not been on stable doses of anticoagulation with low molecular weight heparin or oral anticoagulant for at least two weeks
• History of arterial thromboembolic event in past 6 months (including cerebrovascular accident [CVA], myocardial infarction [MI])
• Systemic anti-cancer treatment within 2 weeks, all ongoing adverse events related to previous systemic anti-cancer therapy resolved to grade =< 1
• Radiotherapy within 2 weeks of first dose of study medications
• Major surgery within 6 weeks of first dose of study medications; minor procedures (e.g. port placement, endoscopy with intervention) within 4 weeks of first dose of study medications
• Presence of Common Terminology Criteria for Adverse Events (CTCAE) grade >= 2 toxicity due to prior cancer therapy (except alopecia, peripheral neuropathy which are excluded if CTCAE grade >= 3)
• Medical condition that requires chronic systemic steroid therapy, or any other form of immunosuppressive medication
• Active ongoing infection requiring therapy; patients with known chronic hepatitis C infection will be allowed if antiviral therapy is not in use; patients with evidence of chronic hepatitis B infection as evidenced by hepatitis B surface antigen positivity and/or evidence of hepatitis B circulating deoxyribonucleic acid (DNA) are required to receive viral prophylaxis while on treatment with entecavir or tenofavir per institutional guidelines; hepatitis viral load studies will be followed as described in protocol
• Active human immunodeficiency virus (HIV) infection
• History of severe hypersensitivity reaction to another monoclonal antibody
• Active central nervous system metastases and/or carcinomatous meningitis (stable treated brain metastases not requiring steroids > 4 weeks allowed)
• Cardiac conditions: class 3-4 New York Heart Association congestive heart failure, known baseline left ventricular ejection fraction (LVEF) < 50%, transmural myocardial infarction, uncontrolled hypertension, angina pectoris requiring medication, clinically significant valvular disease, high-risk arrhythmia in the past 12 months; Note: a baseline echocardiogram (ECHO) is not required for this study unless clinically indicated
• Any history of autoimmune disease requiring treatment in the past 5 years or felt to be at risk to reactivate autoimmune disease; patients who are felt to no longer be at risk of activating a known autoimmune disease (e.g. type 1 diabetes, ulcerative colitis s/p complete colectomy, autoimmune thyroiditis s/p thyroidectomy or medical ablation, etc.) may be allowed to participate after discussion with the principal investigator (PI)
• Pregnant, breast feeding, or planning to become pregnant
• Women of childbearing potential (WOCBP) must agree to follow instructions for method(s) of contraception for the duration of study treatment with nivolumab and 5 months after the last dose of study treatment i.e., 30 days (duration of ovulatory cycle) plus the time required for the investigational drug to undergo approximately five half-lives
• Males who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for the duration of study treatment with nivolumab and 7 months after the last dose of study treatment i.e., 90 days (duration of sperm turnover) plus the time required for the investigational drug to undergo approximately five half-lives
• Received any live vaccine within the last 30 days
• Other malignancy requiring treatment in the prior 2 years with the exception of locally treated squamous or basal cell carcinoma