GNOS-PV02 Personalized Neoantigen Vaccine and Plasmid Encoded IL-12 (INO-9012) Versus Active Surveillance in Subjects With High-Risk HCC (IMPACT 31)

IMPACT 31: A Randomized Open-label, Multi-center, Phase II Adjuvant Study of a Personalized Neoantigen DNA Vaccine (GNOS-PV02) and Plasmid Encoded IL-12 (INO-9012) Versus Active Surveillance in Subjects With High-Risk Hepatocellular Carcinoma

This is a randomized, open-label, multi-site Phase II study of a personalized neoantigen DNA vaccine (GNOS-PV02) and plasmid encoded IL-12 (INO-9012) in subjects with histologically or cytologically confirmed diagnosis of HCC based on pathology report, who were eligible to undergo definitive resection, have demonstrated laboratory, radiographic and/or pathologic high-risk criteria for recurrence (described under eligibility), have no evidence of disease (NED) as per MRI approximately 28 days post resection, and are able to provide a tissue sample for personalized neoantigen DNA vaccine development.

Study Overview

• Status: Not yet recruiting
• Conditions: HCC
• Intervention / Treatment: Biological: GNOS-PV02 + INO-9012 delivered by intradermal injection, followed by electroporation; Device: Electroporation Device

• Study Type: Interventional
• Enrollment (Estimated): 90
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins University
      • Contact: Principal Investigator, MD; Phone Number: 410-955-8893; Email: GIClinicalTrials@jh.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Written informed consent
2. ≥18 years of age
3. Histologically or cytologically confirmed diagnosis of HCC (not accepted: fibrolamellar, sarcomatoid, mixed cholangiocarcinoma)
4. Child-Pugh Class A liver score
5. Documented virology status of hepatitis
6. Availability of a representative post-resection tumor tissue sample
7. ECOG performance status of 0 or 1
8. Adequate organ function
9. Women of childbearing potential (WOCBP) and men must be willing to use an adequate method of contraception

Exclusion Criteria:

1. Is currently participating in 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 to baseline
2. Evidence of residual, recurrent, or metastatic disease at randomization
3. Active or history of autoimmune disease or immune deficiency
4. 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
5. Diagnosed additional malignancy within 5 years prior to baseline, except for: (a) non-invasive carcinomas subject to successful curative treatment in the opinion of the investigator which require no further therapy and (b) other malignancies for which subjects have undergone potentially curative therapy and have been considered disease free for at least 3 years prior to screening.
6. Active infection requiring systemic therapy
7. Is pregnant, breastfeeding or expecting to conceive or father children within the study's projected duration
8. History of human immunodeficiency virus (HIV) (HIV I/II antibodies).
9. Co-infection with HBV and hepatitis D viral infection
10. Co-infection with HBV and HCV
11. Has received a live vaccine within 30 days of planned start of study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A; Arm A: GNOS-PV02 + INO-9012 ID followed by electroporation every 3 weeks for 4 doses, then every 9 weeks (Q9W) until week 104, then every 12 weeks (Q12W) until week 260 followed by 3 years follow-up survival	Biological: GNOS-PV02 + INO-9012 delivered by intradermal injection, followed by electroporation; delivered by intradermal injection and electroporation; Device: Electroporation Device; GNOS-PV02 + INO-9012 ID followed by electroporation
No Intervention: Arm B; Arm B: Active Surveillance for 5 years or until recurrence, plus 3 years follow-up survival.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recurrence-free survival	RFS is defined as the time from randomization to any recurrence (local, locoregional, regional or distant), occurrence of new primary HCC, as assessed by the investigator, or death due to any cause, whichever occurs first.	Up to 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and tolerability	Summary adverse events according to CTCAE 6.0	Up to 5 years
Time to extra-hepatic spread or macro-vascular invasion	Time to extra-hepatic spread or macro-vascular invasion (TTEHS/MVI)	Up to 5 years
Overall survival	OS is defined as time from randomization to death of any cause	Up to 5 years on study + 3 years follow up

Collaborators and Investigators

• Sponsor: Geneos Therapeutics

Publications and helpful links

Helpful Links

• Geneos Therapeutics Website - Platform and company information

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): September 1, 2029
• Study Completion (Estimated): June 1, 2032

Study Registration Dates

• First Submitted: July 20, 2026
• First Submitted That Met QC Criteria: July 20, 2026
• First Posted (Actual): July 23, 2026

Study Record Updates

• Last Update Posted (Actual): July 23, 2026
• Last Update Submitted That Met QC Criteria: July 20, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Other Study ID Numbers: GT-31

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Would include IPD in any resulting publication.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes