The proposed study is an open-label, single institution, single arm phase 1b study of neoadjuvant cabozantinib plus nivolumab in patients with locally advanced HCC.

Inclusion Criteria:

1. Must have locally advanced/borderline resectable hepatocellular carcinoma.
2. Must have measurable disease.
3. Age ≥18 years.
4. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
5. Patients must have adequate organ and marrow function defined by study-specified laboratory tests.
6. Patients must have adequate liver remnant and function.
7. Antiviral therapy per local standard of care for hepatitis B.
8. Woman of child bearing potential must have a negative pregnancy test.
9. Must use acceptable form of birth control while on study.
10. Ability to understand and willingness to sign a written informed consent document.

Exclusion Criteria:

1. Fibrolamellar carcinoma or mixed HCC.
2. Chemotherapy, radiotherapy, investigational therapy, or surgery less than 6 months prior to trial registration.
3. Concomitant Anticoagulation therapy.
4. Any GI or pulmonary risks of bleeding.
5. History of HIV Infection.
6. Active co-infection with hepatitis B and hepatitis C.
7. Active co-infection with hepatitis B and hepatitis D.
8. Has a diagnosis of immunodeficiency, or is receiving systemic steroid therapy.
9. History of any autoimmune disease requiring systemic treatment within the past 2 years. Any patient bearing an allograft is not eligible.
10. Any additional malignancies with treatment or life-limiting cancers. Superficial bladder cancer, non-melanoma skin cancers, or low grade prostate cancer not requiring therapy would not exclude participation in this trial.
11. Uncontrolled intercurrent illness.
12. Corrected QT interval calculated by the Fridericia formula.
13. Uncontrolled high blood pressure.
14. Are pregnant or breastfeeding.
15. Any gastrointestinal (GI) disorders.
16. Any certain study-specified heart conditions 6 months prior to enrollment.
17. Major surgery within 2 months before enrollment.
18. Have any evidence of moderate or severe ascites.
19. Any untreated or incompletely treated varices with bleeding or high-risk bleeding.
20. Inability to swallow intact tablets.
21. Known or suspected hypersensitivity to study treatment.