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

NCT04251117 | Active Not Recruiting Phase 1 FDA Drug FDA Device

• 1 other identifier: GT-30
• Study Type: interventional
• Target: 36
• Locations: 2 countries
• Sites: 3

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.

Conditions

HCC

Outcome Measures

Primary Outcomes (3)

• Adverse evets as graded by CTCAE v5.0

  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

  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

  Up to 24 Months

Secondary Outcomes (7)

• 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 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 Disease Control Rate (DCR)

  Up to 24 Months

• Anti-tumor activity as measured by Progression Free Survival (PFS) as assessed by RECIST 1.1

  Up to 24 Months

Study Arms (1)

GNOS-PV02 + INO-9012 + Pembrolizumab

EXPERIMENTAL

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.

Biological: GNOS-PV02; Biological: INO-9012; Drug: Pembrolizumab; Device: CELLECTRA®2000 EP Device

Interventions

GNOS-PV02 BIOLOGICAL

GNOS-PV02 delivered by intradermal injection and electroporation

GNOS-PV02 + INO-9012 + Pembrolizumab

INO-9012 BIOLOGICAL

INO-9012 delivered by intradermal injection and electroporation

GNOS-PV02 + INO-9012 + Pembrolizumab

Pembrolizumab DRUG

Pembrolizumab administered as an intravenous (IV) infusion

GNOS-PV02 + INO-9012 + Pembrolizumab

CELLECTRA®2000 EP Device DEVICE

CELLECTRA® 2000 Device is a system indicated for use to enhance the uptake and expression of plasmid-based biologics in order to enhance vaccine efficacy.

GNOS-PV02 + INO-9012 + Pembrolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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 1.1.
• 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.
• 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 (\<10 IU/ml) do not require anti-viral therapy prior to enrollment however these subjects will be tested at every cycle to monitor HBV DNA levels and initiate antiviral therapy if HBV DNA is detected (≥10 IU/ml). Subjects with chronic infection by hepatitis C virus (HCV), who are untreated, are allowed on study. In addition, subjects with successful HCV treatment (defined as sustained virologic response \[SVR\] 12 or SVR 24) are allowed, as long as 4 weeks have passed between completion of HCV therapy and start of study drug. Subjects receiving antiviral therapy during TKI may be enrolled.
• Women of childbearing potential (WOCBP) must have a negative urine or serum pregnancy test for the patient to be eligible for trial enrolment.
• Be willing to use an adequate method of contraception for the course of the study through 150 days after the last dose of study drug (male and female subjects of childbearing potential).
• Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
• Demonstrate adequate organ function

You may not qualify if:

• 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.
• Has received locoregional therapy to liver (transarterial chemoembolization \[TACE\], transarterial embolization \[TAE\], radiation, radioembolization, or ablation) or major surgery to liver or other site within 3 weeks prior to the first dose of study drug. Minor surgery (e.g., simple excision, tooth extraction) must have occurred at least 7 days prior to the first dose of study drug (Cycle 1, Day 1). Subjects must have recovered adequately (i.e., Grade ≤1 or baseline) from the toxicity and/or complications from any intervention prior to starting therapy.
• Has a diagnosed additional malignancy within 5 years prior to first dose of study drug, with the exception of curatively treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin, and/or curatively resected in situ cervical and/or breast cancers. Subjects with history of early-stage prostate cancer that has been curatively treated or appropriate for observation may be enrolled.
• Has radiographically detectable (even if asymptomatic and/or previously treated) central nervous system (CNS) metastases and/or carcinomatous meningitis, as assessed by local site investigator.
• Has a known history of, or any evidence of, interstitial lung disease or active non- infectious pneumonitis.
• Has an active infection requiring systemic therapy.

Sponsors & Collaborators

• Geneos Therapeutics: lead

Study Sites (3)

Johns Hopkins Hospital

Baltimore, Maryland, 21287, United States

Location

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

Auckland Clinical Studies

Auckland, New Zealand

Location

Related Publications (1)

• Yarchoan M, Gane EJ, Marron TU, Perales-Linares R, Yan J, Cooch N, Shu DH, Fertig EJ, Kagohara LT, Bartha G, Northcott J, Lyle J, Rochestie S, Peters J, Connor JT, Jaffee EM, Csiki I, Weiner DB, Perales-Puchalt A, Sardesai NY. Personalized neoantigen vaccine and pembrolizumab in advanced hepatocellular carcinoma: a phase 1/2 trial. Nat Med. 2024 Apr;30(4):1044-1053. doi: 10.1038/s41591-024-02894-y. Epub 2024 Apr 7.

  PMID: 38584166 RESULT

Related Links

• Nature Medicine

MeSH Terms

Interventions

rocakinogene sifuplasmid; pembrolizumab

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 27, 2020
• First Posted: January 31, 2020
• Study Start: March 1, 2020
• Primary Completion: November 29, 2024
• Study Completion (Estimated): November 29, 2028
• Last Updated: April 22, 2026

Record last verified: 2026-04

Locations

NZ (1); US (2)