Cabozantinib and Pembrolizumab for the First-Line Treatment of Advanced Liver Cancer

Inclusion Criteria: * Must have a histologically confirmed diagnosis of HCC or a non-invasive diagnosis of HCC as per the American Association for the Study of Liver Diseases (AASLD) criteria * If available, archival tissue must be submitted * Mixed HCC-cholangiocarcinoma is not allowed * Patient has Barcelona Clinic Liver Cancer (BCLC) stage C disease, or BCLC stage B disease that is not amenable to locoregional therapy or refractory to locoregional therapy, and not amenable to curative treatment * Previous locoregional therapy is allowed (e.g. surgical resection, external beam radiation, catheter-based therapy), and patients must have evidence of disease progression from locoregional therapy * Must have measurable disease by RECIST v1.1 * Lesions that were previously radiated or ablated cannot be target lesions unless there was subsequent radiographic progression at those sites * No prior systemic therapy for HCC. Prior chemotherapy given locally into the liver (e.g. transarterial chemoembolization \[TACE\]) is allowed * Must have Child-Pugh class A hepatic function within 7 days prior to first dose of study intervention * Eastern Cooperative Oncology Group (ECOG) performance status 0-1 * Life expectancy of at least 12 weeks * Recovery to baseline or =\< grade 1 toxicities (CTCAE v5) related to any prior treatments, unless adverse events (AEs) are clinically nonsignificant and/or stable on supportive therapy * Absolute neutrophil count (ANC) \>= 1500/mm\^3 witho…