GNOS-PV02 Personalized Neoantigen Vaccine, INO-9012 and Pembrolizumab in Subjects With Advanced HCC

This is a single-arm, open-label, multi-site Phase I/IIa study of a personalized neoantigen DNA vaccine (GNOS-PV02) and plasmid encoded IL-12 (INO-9012) in combination with pembrolizumab (MK-3475) in subjects with histologically or cytologically confirmed diagnosis of HCC based on pathology report.

Inclusion Criteria: 1. Be willing and able to provide written informed consent for the study. The subject may also provide consent for Future Biomedical Research (FBR). However, the subject may participate in the main study without participating in FBR. 2. 18 years of age on day of signing informed consent. 3. Have histologically or cytologically confirmed diagnosis of HCC based on pathology report. Radiological diagnosis is valid to initiate screening pending confirmation by pathology. 4. Have Barcelona Clinic Liver Cancer (BCLC) Stage C disease or BCLC Stage B disease not amenable to locoregional therapy, or refractory to locoregional therapy, and not amenable to a curative treatment approach. 5. Have a Child-Pugh Class A liver score. 6. Have a predicted life expectancy of greater than 6 months. 7. Have measurable disease based on RECIST 1.1. 8. Have a performance status of 0 or 1 using the ECOG Performance Scale within 7 days of first dose of study drug. 9. Receiving or eligible for first-line therapy with sorafenib or lenvatinib. 10. Willing to submit a tissue sample for personalized DNA vaccine manufacturing. 11. Patients with chronic or acute HBV infection \[as characterized by positive hepatitis B surface antigen (HBsAg) and/or hepatitis B core antibodies (anti-HBcAb) with detectable HBV DNA (≥10 IU/ml)\] must be treated with effective antiviral therapy, as per institutional practices, prior to enrollment and for the duration of the study therapy. Patients who test positive for anti-hepatitis B core (HBc) with undetectable HBV DNA (\