Feasibility and Efficacy of Perioperative Nivolumab With or Without Relatlimab for Patients With Potentially Resectable Hepatocellular Carcinoma (HCC)

Inclusion Criteria:

• Technically resectable HCC as defined by:

• HCC may be diagnosed pathologically, or noninvasively by the American Associationfor the Study of Liver Diseases (AASLD) criteria or the Organ Procurement andTransplant Network (OPTN) Obligatory Diagnostic Criteria for HepatocellularCarcinoma (HCC).

No extrahepatic spread, no nodal disease, and no bilateral left and right branch portal vein involvement.

• Measurable disease per RECIST 1.1 as determined by the investigator.

• Age ≥ 18 years old on the day of consent.

• ECOG performance status ≤1 or Karnofsky ≥80.

• Patients must have adequate organ and marrow function defined by study-specifiedlaboratory tests prior to initial study drug.

• Patients must have adequate liver remnant and function.

• Antiviral therapy per local standard of care for hepatitis B.

• LVEF assessment with documented LVEF ≥ 50% by either TTE or MUGA (TTE preferred)within 6 months from first study drug administration.

• Woman of child-bearing potential must have a negative pregnancy test.

• Must use acceptable form of birth control while on study.

• Ability to understand and willingness to sign a written informed consent document.

Exclusion Criteria:

• Fibrolamellar carcinoma or mixed HCC.

• Receiving, or previously received, any systemic chemotherapy, or investigationalagent for HCC.

• Patients with a history of prior treatment with anti-PD-1, anti-PD-L1, anti-PD-L2,anti-CTLA4, or anti-Lag-3 antibodies.

• Has a known additional malignancy that is expected to require active treatmentwithin two years, or is likely to be life-limiting in the opinion of the treatinginvestigator. Superficial bladder cancer, non-melanoma skin cancers, or low gradeprostate cancer not requiring therapy would not exclude participation in this trial.

• History of HIV infection.

• Active co-infection with HBV and HDV.

• Has a diagnosis of immunodeficiency, or is receiving systemic steroid therapy.

• Prior tissue or organ allograft or allogeneic bone marrow transplantation.

• History of any autoimmune disease requiring systemic treatment within the past 2years.

• Systemic or topical corticosteroids at immunosuppressive doses (> 10 mg/day ofprednisone or equivalent).

• Confirmed history of encephalitis, meningitis, or uncontrolled seizures in the yearprior to informed consent.

• Uncontrolled intercurrent illness.•

• Uncontrolled or significant cardiovascular disease.

• Significant heart disease.

• Moderate or severe ascites.

• Known or suspected hypersensitivity to study treatment.

• Are pregnant or breastfeeding.

• WOCBP and men with female partners (WOCBP) who are not willing to use contraception.

• Unable to have blood drawn.

• Any other sound medical, psychiatric, and/or social reason as determined by theInvestigator.

• Any illicit drugs or other substance abuse.