Sorafenib and Nivolumab in Treating Participants With Unresectable, Locally Advanced or Metastatic Liver Cancer

Inclusion Criteria

• Histologic or cytologic diagnosis of unresectable, locally advanced and/or metastatic hepatocellular carcinoma (HCC) not amenable to curative surgery, transplantation, or ablative therapies based upon assessment of treating investigator.

a. For patients without prior histologic or cytologic diagnosis, radiographic diagnosis is allowed provided patients meet American Association for the Study of Liver Diseases (AASLD) criteria for radiographic diagnosis.

• Radiographically measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 in at least one site not previously treated with chemoembolization, radioembolization, radiation, or other local/liver-directed procedures (i.e. must have at least one measurable target lesion, either within the liver or in a measurable metastatic site); a new area of tumor progression within or adjacent to a previously-treated lesion, if clearly measurable by a radiologist, is acceptable.
• Untreated/pretreatment archival tumor tissue must be available for correlative analyses
• Age at least 18 years at enrollment.
• Eastern Cooperative Oncology Group (ECOG) 0 or 1 at enrollment
• At least 4 weeks after any prior chemoembolization, radioembolization, local ablative therapies, or hepatic radiation and recovery to = = 60 mL/min.
• Child-Pugh A or B7 (Part 1); Child-Pugh B7-9 (Part 2).
• If HBV surface antigen (sAg) and/or core antibody (Ab) positive, must be treated with appropriate antiviral therapy according to institutional practice with HBV deoxyribonucleic acid (DNA) by polymerase chain reaction (PCR) less than 500 IU/mL.
• If clinical or histologic diagnosis of cirrhosis and/or clinical or radiographic evidence esophageal or gastric varices, must have had esophagogastroduodenoscopy (EGD) surveillance and adequate endoscopic therapy according to institutional standards.
• Able to swallow and retain oral medications
• Women of child-bearing potential (WOCBP) must have a negative pregnancy test within 28 days before study enrollment.
• WOCBP and male partners of WOCBP must agree to use two methods of contraception until at least 5 months after last dose of each study drug for WOCBP subjects, and 7 months for male partners of WOCBP.
• Able to understand and willingness to provide informed consent, and the willingness to comply with the requirements of the protocol.
• Subjects must have signed and dated an Institutional Review Board (IRB)/Independent Ethics Committees (IEC) approved written informed consent form in accordance with regulatory and institutional guidelines and before the performance of any protocol related procedures that are not part of standard of care.

Exclusion Criteria

• Any prior systemic therapy for HCC.
• Known fibrolamellar or mixed HCC-cholangiocarcinoma histology.
• Requirement for paracentesis to control ascites within 6 months before enrollment.

a. Ascites which is not clinically detectable or mild on stable doses of diuretics during screening is allowed provided meets criteria for Child Pugh A or B7 (Part 1) or B7-9 (Part 2).

• Symptomatic hepatic encephalopathy requiring medication (such as lactulose or rifaximin) (Part 1) or any hospitalization for encephalopathy within 6 months before enrollment (Part 1 or 2).
• Hepatic encephalopathy that is adequately controlled on stable doses of lactulose and/or rifaximin per assessment of treating investigator is allowed in Part 2, provided no hospitalization for encephalopathy within 6 months before enrollment.
• Medications such as lactulose used for other indications (e.g. constipation) are allowed in both Part 1 and 2.
• History of upper gastrointestinal (GI) bleeding from esophageal and/or gastric varices within 12 months before enrollment.
• Requirement for systemic corticosteroids unless used for adrenal replacement, acute therapy for asthma or bronchitis exacerbation (= 140 mm Hg and/or diastolic pressure > 90 mm Hg (National Cancer Insti