Trial Review

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT04251117




Registration number
NCT04251117
Ethics application status
Date submitted
27/01/2020
Date registered
31/01/2020
Date last updated
19/04/2024

Titles & IDs
Public title
GNOS-PV02 Personalized Neoantigen Vaccine, INO-9012 and Pembrolizumab in Subjects With Advanced HCC
Scientific title
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
Secondary ID [1] 0 0
GT-30
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
HCC 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - GNOS-PV02
Other interventions - INO-9012
Treatment: Drugs - Pembrolizumab
Treatment: Devices - CELLECTRA®2000 EP Device

Experimental: 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.


Other interventions: GNOS-PV02
GNOS-PV02 delivered by intradermal injection and electroporation

Other interventions: INO-9012
INO-9012 delivered by intradermal injection and electroporation

Treatment: Drugs: Pembrolizumab
Pembrolizumab administered as an intravenous (IV) infusion

Treatment: Devices: CELLECTRA®2000 EP 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.
Intervention code [1] 0 0
Other interventions
Intervention code [2] 0 0
Treatment: Drugs
Intervention code [3] 0 0
Treatment: Devices
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Adverse evets as graded by CTCAE v5.0
Timepoint [1] 0 0
Up to 24 Months
Primary outcome [2] 0 0
Immunogenicity of a personalized neoantigen DNA vaccine as measured by interferon-? secreting T lymphocytes in peripheral blood mononuclear cells (PBMCs) using ELISpot
Timepoint [2] 0 0
Up to 24 Months
Primary outcome [3] 0 0
Immunogenicity of a personalized neoantigen DNA vaccine as measured by T-cell activation and cytolytic cell phenotype in PBMCs using Flow Cytometry
Timepoint [3] 0 0
Up to 24 Months
Secondary outcome [1] 0 0
Anti-tumor activity as measured by Objective Response Rate (ORR) by RECIST 1.1 by investigator review
Timepoint [1] 0 0
Up to 24 Months
Secondary outcome [2] 0 0
Anti-tumor activity as measured by ORR by iRECIST
Timepoint [2] 0 0
Up to 24 Months
Secondary outcome [3] 0 0
Anti-tumor activity as measured by Duration of Response (DOR)
Timepoint [3] 0 0
Up to 24 Months
Secondary outcome [4] 0 0
Anti-tumor activity as measured by Disease Control Rate (DCR)
Timepoint [4] 0 0
Up to 24 Months
Secondary outcome [5] 0 0
Anti-tumor activity as measured by Progression Free Survival (PFS) as assessed by RECIST 1.1
Timepoint [5] 0 0
Up to 24 Months
Secondary outcome [6] 0 0
Anti-tumor activity as measured by Progression Free Survival (PFS) as assessed by iRECIST
Timepoint [6] 0 0
Up to 24 Months
Secondary outcome [7] 0 0
Anti-tumor activity as measured by Overall Survival (OS)
Timepoint [7] 0 0
Up to 24 Months

Eligibility
Key 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 (<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.

12. Women of childbearing potential (WOCBP) must have a negative urine or serum pregnancy
test for the patient to be eligible for trial enrolment.

13. 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.

14. Demonstrate adequate organ function
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. 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.

2. Has received sorafenib or lenvatinib within 14 days of first dose of study drug.

3. 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.

4. Has clinically apparent ascites on physical examination. Note: only ascites detectable
on imaging studies is allowed.

5. Evidence of portal vein invasion based on imaging is allowed pending subjects meet
laboratory criteria for enrollment.

6. Has had encephalopathy in the last 6 months. Subjects on rifaximin or lactulose to
control their encephalopathy are not allowed.

7. Had a solid organ or hematologic transplant.

8. Had prior systemic therapy for HCC other than sorafenib or lenvatinib.

9. 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.

10. 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.

11. 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.

12. 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.

13. 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.

14. Has a known history of, or any evidence of, interstitial lung disease or active non-
infectious pneumonitis.

15. Has an active infection requiring systemic therapy.

16. Has a history or current evidence of any condition, therapy, or laboratory abnormality
that might confound the results of the study, interfere with the subject's
participation for the full duration of the study, or is not in the best interest of
the subject to participate, in the opinion of the treating investigator, including
dialysis.

17. Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the study.

18. Is pregnant or breastfeeding or expecting to conceive or father children within the
projected duration of the study, starting with the screening visit through 150 days
after the last dose of study drug.

19. Has received prior immunotherapy including anti-programmed death (PD) 1,
anti-programmed death ligand (PD-L)-1, or anti-PD-L2 agents, or personalized therapies
such as adoptive cell therapy or neoantigen-based vaccine.

20. Has a known history of human immunodeficiency virus (HIV) (HIV I/II antibodies).

21. Has untreated active hepatitis B virus (HBV), unless planned antiviral therapy during
TKI.

Note: Patients with HBV infection, characterized by positive HBsAg and/or HBcAb with
detectable HBV DNA (=10 IU/ml or above the limit of detection per local lab standard),
must be treated with antiviral therapy as per institutional practice to ensure
adequate viral suppression (HBV DNA =2000 IU/mL) prior to treatment with the study
drug. Patients who test positive for HBcAg with undetectable HBV DNA (<10 IU/ml or
under the limit of detection per local lab standard) do not require anti-viral therapy
prior to enrollment.

22. Has received a live vaccine within 30 days of planned start of study treatment (Cycle
1, Day 1).

Note: The killed virus vaccines used for seasonal influenza vaccines for injection are
allowed; however intranasal influenza vaccines (e.g., FluMist®) are live attenuated
vaccines and are not allowed. Non-live COVID-19 vaccines are allowed.

23. Any contraindication for treatment with the CELLECTRA® 2000 Device:

Less than two acceptable sites available for ID injection and EP considering the
deltoid and anterolateral quadriceps muscles:

1. Tattoos, keloids or hypertrophic scars located within 2 cm of intended
administration site.

2. Implantable-Cardioverter-defibrillator (ICD) or pacemaker (to prevent a
life-threatening arrhythmia) that is located ipsilateral to the deltoid injection
site (unless deemed acceptable by a cardiologist).

3. Any metal implants or implantable medical device within the intended treatment
site (i.e. electroporation area).

24. Has no mutations detected after sequencing of the tumor

Study design
Purpose of the study
Treatment
Allocation to intervention
N/A
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1/Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/03/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/06/2025
Actual
Sample size
Target
36
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Maryland
Country [2] 0 0
United States of America
State/province [2] 0 0
New York
Country [3] 0 0
New Zealand
State/province [3] 0 0
Auckland

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Geneos Therapeutics
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT04251117
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT04251117