Nivolumab and Bevacizumab in Patients With Advanced and or Metastatic Hepatocellular Carcinoma

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 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 RECIST1.1.
* Age ≥18 years.
* ECOG performance status of 0 to 1.
* Life expectancy ≥ 12 weeks.
* Childs Pugh A (5-6 points). Demonstrate adequate organ function as defined in the table below

Hematologic:

Absolute neutrophil count (ANC) ≥ 1.5 k/µL. Platelets ≥ 100 k/µL Hemoglobin ≥ 9 g/dL

Renal:

Creatinine \< 2 × ULN OR

\- 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 DVT/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 CVA, 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 ≥ 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.
* Active 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 LVEF \< 50%, transmural myocardial infarction, uncontrolled hypertension, angina pectoris requiring medication, clinically significant valvular disease, high-risk arrhythmia in the past 12 months.
* 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 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. Contraception as described in section 7.3
* 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. Contraception as described in section 7.3
* 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.