Clinical Trials /

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

NCT04251117

Description:

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.

Related Conditions:
  • Hepatocellular Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: GNOS-PV02 Personalized Neoantigen Vaccine, INO-9012 and Pembrolizumab in Subjects With Advanced HCC
  • Official 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

Clinical Trial IDs

  • ORG STUDY ID: GT-30
  • NCT ID: NCT04251117

Conditions

  • HCC

Interventions

DrugSynonymsArms
GNOS-PV02GNOS-PV02 + INO-9012 + Pembrolizumab
INO-9012GNOS-PV02 + INO-9012 + Pembrolizumab
PembrolizumabGNOS-PV02 + INO-9012 + Pembrolizumab

Purpose

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 Arms

NameTypeDescriptionInterventions
GNOS-PV02 + INO-9012 + PembrolizumabExperimentalFirst 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.
  • GNOS-PV02
  • INO-9012
  • Pembrolizumab

Eligibility Criteria

        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. Have a negative urine or serum pregnancy test within 72 hours prior to receiving the
             first dose of study drug (Cycle 1, Day 1) (female subjects of childbearing potential).
             If the urine test is positive, or cannot be confirmed as negative, a serum pregnancy
             test will be required.

         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.

        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.

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

               -  Any significant acute or chronic medical illness if deemed by the practitioner
                  that EP treatment could negatively impact the illness

               -  Presence of unstable or life-threatening cardiac disease (e.g., unstable angina,
                  Class 3 or higher congestive heart failure).

               -  A cardioverter-defibrillator or pacemaker (to prevent a life-threatening
                  arrhythmia) that is located ipsilateral to the intended deltoid injection site
                  (unless deemed acceptable by a cardiologist).

               -  Any metal implants or implantable medical device within the electroporation area.

         24. Has no mutations detected after sequencing of the tumor
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Adverse evets as graded by CTCAE v5.0
Time Frame:Up to 24 Months
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Anti-tumor activity as measured by Objective Response Rate (ORR) by RECIST 1.1 by investigator review
Time Frame:Up to 24 Months
Safety Issue:
Description:
Measure:Anti-tumor activity as measured by ORR by iRECIST
Time Frame:Up to 24 Months
Safety Issue:
Description:
Measure:Anti-tumor activity as measured by Duration of Response (DOR)
Time Frame:Up to 24 Months
Safety Issue:
Description:
Measure:Anti-tumor activity as measured by Disease Control Rate (DCR)
Time Frame:Up to 24 Months
Safety Issue:
Description:
Measure:Anti-tumor activity as measured by Progression Free Survival (PFS) as assessed by RECIST 1.1
Time Frame:Up to 24 Months
Safety Issue:
Description:
Measure:Anti-tumor activity as measured by Progression Free Survival (PFS) as assessed by iRECIST
Time Frame:Up to 24 Months
Safety Issue:
Description:
Measure:Anti-tumor activity as measured by Overall Survival (OS)
Time Frame:Up to 24 Months
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Geneos Therapeutics

Last Updated

January 30, 2020