Background: Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and is responsible for more than 500,000 deaths annually. Bavi, a monoclonal antibody designed to inhibit the immunosuppressive effects of phosphatidylserine through interaction with TIM and TAM receptor family members in the tumor microenvironment (TME), is being evaluated in combination with pembro, a monoclonal antibody designed to inhibit Programmed cell death protein 1 (PD-1), in patients with advanced HCC. Methods: This phase 2, open-label, multi-site trial included patients with histologically confirmed locally advanced or metastatic HCC who have not received prior systemic therapy. Patients were treated with pembro (200 mg Q3W) in combination with bavi (3 mg/kg QW) until disease progression. The primary endpoint of the trial is confirmed ORR by RECIST 1.1. A minimax two-stage method to analyze ORR after 15 patients and enroll an additional 13 patient if 3 or more responses observed in first 15 patients (NCT03519997). Results: Three out of 15 evaluable patients responded during Stage 1, allowing for enrollment to continue with a planned 13 additional patients in Stage 2. The study completed enrollment after a total of 28 patients were determined to be evaluable. The confirmed ORR based upon data from 28 patients evaluable for response was 32% (9 confirmed, partial responses). The disease control rate was 61% (9 partial responses, 8 stable disease). The safety profile of pembro plus bavi was consistent with the established profiles of individual drugs and updated adverse events will be reported at the time of presentation along with correlative studies. Conclusions: The combination of bavi and pembro appears to be well tolerated in this patient population and has a toxicity profile comparable to monotherapy immune checkpoint inhibitor. Preliminary analyses suggests that bavi and pembro may have promising anti-tumor activity in advanced HCC. Clinical trial information: NCT03519997.