A Study of Pembrolizumab and Bavituximab in Patients With Advanced Hepatocellular Carcinoma

This is a non-randomized, open-label, multi-site phase II therapeutic trial of pembrolizumab and bavituximab in patients with locally advanced HCC. Locally advanced or metastatic HCC is defined as disease that is not amenable to surgical and/or locoregional therapies. Subjects must not have received prior systemic therapy for advanced HCC in keeping with the first-line setting of this study. Overall response rate (ORR) as assessed by the investigators and using RECIST 1.1 criteria, will be the primary endpoint.

Prior to initiation on treatment, all patients will sign an informed consent form. Only patients with histological proved HCC will be eligible for treatment. Tissue, either from archival formalin fixed paraffin embedded samples or a new biopsy of a target lesion will be needed.

Study therapy is defined as treatment with both pembrolizumab and bavituximab. Patients will receive trial treatment until disease progression, unacceptable toxicity, death or discontinuation from the study treatment for any other reason. Subjects will be allowed to continue study therapy after an initial investigator-assessed RECIST 1.1 defined progression as long as they meet the following criteria: 1) investigator assessed clinical benefit and 2) subject is tolerating study therapy. Subjects will be discontinued from study therapy upon the evidence of further progression, defined as an additional 10% or greater increase in tumor burden from time of initial progression (including all target lesions and new measurable lesions). New lesions are considered measurable if the longest diameter is at least 10 mm (except for pathological lymph nodes, which must have a short axis of at least 15 mm). Any new lesion considered non-measurable may become measurable and therefore included in the tumor burden measurement if the longest diameter increases to at least 10 mm (except for pathological lymph nodes, which must have an increase in short axis to at least 15 mm. For statistical analyses that include the investigator-assessed progression date, subjects who continue treatment beyond initial investigator-assessed, RECIST 1.1-defined progression will be considered to have investigator-assessed progressive disease at the time of the initial progressive event irrespective of confirmation on subsequent imaging. Patients will be followed for survival regardless of treatment discontinuation for any reason, unless they withdraw their consent to be followed for survival.

Treatment Phase

The treatment phase for each patient will begin on the initiation of study drug on Cycle 1 Day 1 (C1D1). Patients will continue study treatment until disease progression (or until discontinuation of study therapy in patient receiving pembrolizumab and bavituximab beyond progression), discontinuation due to toxicity, withdrawal of consent, or the study ends. A safety follow-up is mandatory at 30 days post the last dose.