An Open-label, Multi-center, 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 Advanced Hepatocellular Carcinoma
Overview
- Phase
- Phase 1
- Status
- Active, not recruiting
- Sponsor
- Geneos Therapeutics
- Enrollment
- 36
- Locations
- 5
- Primary Endpoint
- Adverse evets as graded by CTCAE v5.0
Overview
Brief Summary
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.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •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.
- •18 years of age on day of signing informed consent.
- •Have histologically or cytologically confirmed diagnosis of HCC based on pathology report. Radiological diagnosis is valid to initiate screening pending confirmation by pathology.
- •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.
- •Have a Child-Pugh Class A liver score.
- •Have a predicted life expectancy of greater than 6 months.
- •Have measurable disease based on RECIST 1.
- •Have a performance status of 0 or 1 using the ECOG Performance Scale within 7 days of first dose of study drug.
- •Receiving or eligible for first-line therapy with sorafenib or lenvatinib.
- •Willing to submit a tissue sample for personalized DNA vaccine manufacturing.
Exclusion Criteria
- •Is currently participating and receiving study drug or has participated in a study of an investigational agent and received study drug or used an investigation device, within 4 weeks of the first dose of treatment. Subjects must also have recovered from associated therapy (i.e., to Grade ≤1 or baseline) and from AEs due to any prior therapy.
- •Has received sorafenib or lenvatinib within 14 days of first dose of study drug.
- •Has had esophageal or gastric variceal bleeding within the last 6 months. If suspected, subjects will be screened for esophageal varices. If varices are present, they should be treated according to institutional standards before starting study treatment.
- •Has clinically apparent ascites on physical examination. Note: only ascites detectable on imaging studies is allowed.
- •Evidence of portal vein invasion based on imaging is allowed pending subjects meet laboratory criteria for enrollment.
- •Has had encephalopathy in the last 6 months. Subjects on rifaximin or lactulose to control their encephalopathy are not allowed.
- •Had a solid organ or hematologic transplant.
- •Had prior systemic therapy for HCC other than sorafenib or lenvatinib.
- •Has active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., T4, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
- •Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug. The use of physiologic doses of corticosteroids may be approved after consultation with the Sponsor.
Arms & Interventions
GNOS-PV02 + INO-9012 + Pembrolizumab
First line therapy with standard of care tyrosine kinase inhibitors (TKI) during which patient-specific GNOS-PV02 will be manufactured.
GNOS-PV02 + INO-9012 + Pembrolizumab will be administered upon disease progression or intolerance to TKI.
Intervention: GNOS-PV02 (Biological)
GNOS-PV02 + INO-9012 + Pembrolizumab
First line therapy with standard of care tyrosine kinase inhibitors (TKI) during which patient-specific GNOS-PV02 will be manufactured.
GNOS-PV02 + INO-9012 + Pembrolizumab will be administered upon disease progression or intolerance to TKI.
Intervention: INO-9012 (Biological)
GNOS-PV02 + INO-9012 + Pembrolizumab
First line therapy with standard of care tyrosine kinase inhibitors (TKI) during which patient-specific GNOS-PV02 will be manufactured.
GNOS-PV02 + INO-9012 + Pembrolizumab will be administered upon disease progression or intolerance to TKI.
Intervention: CELLECTRA®2000 EP Device (Device)
GNOS-PV02 + INO-9012 + Pembrolizumab
First line therapy with standard of care tyrosine kinase inhibitors (TKI) during which patient-specific GNOS-PV02 will be manufactured.
GNOS-PV02 + INO-9012 + Pembrolizumab will be administered upon disease progression or intolerance to TKI.
Intervention: Pembrolizumab (Drug)
Outcomes
Primary Outcomes
Adverse evets as graded by CTCAE v5.0
Time Frame: Up to 24 Months
Immunogenicity of a personalized neoantigen DNA vaccine as measured by interferon-γ secreting T lymphocytes in peripheral blood mononuclear cells (PBMCs) using ELISpot
Time Frame: Up to 24 Months
Immunogenicity of a personalized neoantigen DNA vaccine as measured by T-cell activation and cytolytic cell phenotype in PBMCs using Flow Cytometry
Time Frame: Up to 24 Months
Secondary Outcomes
- Anti-tumor activity as measured by ORR by iRECIST(Up to 24 Months)
- Anti-tumor activity as measured by Duration of Response (DOR)(Up to 24 Months)
- Anti-tumor activity as measured by Progression Free Survival (PFS) as assessed by RECIST 1.1(Up to 24 Months)
- Anti-tumor activity as measured by Progression Free Survival (PFS) as assessed by iRECIST(Up to 24 Months)
- Anti-tumor activity as measured by Objective Response Rate (ORR) by RECIST 1.1 by investigator review(Up to 24 Months)
- Anti-tumor activity as measured by Disease Control Rate (DCR)(Up to 24 Months)
- Anti-tumor activity as measured by Overall Survival (OS)(Up to 24 Months)