PRIMARY OBJECTIVE:~I. To evaluate the safety and tolerability of therapy and assess the pathologic response rate including pathologic complete response (pCR) and degree of necrosis (> 50% in tumor volume) with nivolumab + pegargiminase (ADI-PEG 20) in resectable hepatocellular carcinoma (HCC) in the context of presurgical therapy.~SECONDARY OBJECTIVE:~I. To assess the efficacy of presurgical nivolumab + ADI-PEG 20 therapy in HCC by estimating the time-to-progression (TTP), recurrence-free survival (RFS), and overall survival (OS).~EXPLORATORY OBJECTIVES:~I. To assess the immunological/biomarker changes (pre- versus [vs] post-treatment) in tumor tissues and peripheral blood in response to nivolumab + ADI-PEG 20 in HCC therapy.~II. To explore any potential association between these biomarker measures and antitumor response and immune-related response criteria (irRC) assessed by MD Anderson Department of Diagnostic Imaging.~OUTLINE:~Patients receive nivolumab intravenously (IV) over 30 minutes on day 1 and pegargiminase intramuscularly (IM) at 2 days before day 1 of cycle 1, day 8 of cycle 1, days 1 and 8 of cycle 2, and day 1 of cycle 3. Treatments repeat every 2 weeks for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo standard of care surgical resection at week 7.~After completion of study treatment, patients are followed up at 30 days, then every 12 weeks for up to 2 years.
This phase II trial studies the effect of nivolumab and ADI-PEG 20 before surgery in treating patients with liver cancer that can be removed by surgery (resectable). Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. ADI-PEG 20 may stop the growth of tumor cells by blocking some of the proteins needed for cell growth. Giving nivolumab and ADI-PEG 20 before surgery may help control liver cancer.