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This is a single-arm, open-label, multi-center Phase 2 clinical study to evaluate the efficacy and safety of Glypican3 (GPC3)-targeted DNA plasmid vaccine (NWRD06) in patients with GPC3-positive primary hepatocellular carcinoma after curative resection.
Eligible subjects will receive three injections of 4 mg NWRD06 at Weeks 0, 4, and 8. All enrolled subjects will be assessed by tumor imaging at Weeks 12, 24, 36, 48, and 72 after the first dose. These assessments will continue until the first occurrence of any of the following: disease recurrence, meeting withdrawal criteria, initiation of new antitumor therapy, or the completion of Week 72.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 4mg of NWRD06/dose | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| NWRD06 administered by electroporation | Biological | DNA plasmid delivered via IM injection + electroporation using TERESA device |
|
| Measure | Description | Time Frame |
|---|---|---|
| Recurrence-free survival rate after treatment with NWRD06 in patients with resected hepatocellular carcinoma. | The number of participants who are recurrence-free at Week 72 after treatment with NWRD06. | Week 72 |
| Measure | Description | Time Frame |
|---|---|---|
| Recurrence-free survival after treatment with NWRD06 in patients with resected hepatocellular carcinoma. | Duration of recurrence-free survival in hepatocellular carcinoma patients after curative resection and treatment with NWRD06. | up to 72 weeks |
| Incidence and severity of local and systemic adverse events (AEs). |
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Inclusion Criteria:
2) Surgical margin negative. 8. No Vp4 macrovascular invasion, hepatic vein or inferior vena cava macrovascular invasion of any grade after radical resection; Notes: Patients with Vp1, Vp2, or Vp3 macrovascular invasion confirmed by imaging or pathology are eligible.
9. ECOG Performance Status of 0 or 1 within 1 week prior to the first dose. 10. Child-Pugh score A/B (≤7) within 1 week prior to the first dose. 11. Adequate organ function within 1 week prior to the first dose: 1) Blood routine: Hemoglobin (Hb) ≥90 g/L; Platelet count (PLT) ≥75×109/L; 2) Liver: Total bilirubin (TB) ≤3× upper limit of normal (ULN); Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤5×ULN; Plasma albumin ≥30g/L; 3) Coagulation: International Normalized Ratio (INR) ≤2.3. 4) Renal: Serum Creatinine (Scr) ≤1.5 × ULN, OR Creatinine Clearance ≥40 mL/min (if Scr >1.5 × ULN).
12. The expected survival time is more than 6 months; 13. Patients with non-viral primary HCC meet the inclusion criteria. For patients with Hepatitis B virus-related primary HCC(HBV-HCC) or Hepatitis C virus-related primary HCC(HCV-HCC), concurrent antiviral therapy is required.
14. Female subjects of childbearing potential must have a negative serum pregnancy test within 1 week prior to the first dose and must agree to use highly effective contraception from the start of the study treatment until the end of the study. Male subjects must be surgically sterile or must agree to use highly effective contraception during the same period.
15. Have fully understood the study and voluntarily signed the ICF, have good communication with the investigator, and are able to complete all treatments, examinations, and visits stipulated in the study protocol.
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Zhen Huang, M.D. | Contact | 86-010-87787100 | huangzhen@cicams.ac.cn |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Beijing You'an Hospital, Capital Medical University | Not yet recruiting | Beijing | Beijing Municipality | 100000 | China |
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| ID | Term |
|---|---|
| D006528 | Carcinoma, Hepatocellular |
| ID | Term |
|---|---|
| D000230 | Adenocarcinoma |
| D002277 | Carcinoma |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009370 | Neoplasms by Histologic Type |
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Based on the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) V5.0, adverse events (AEs) and serious adverse events (SAEs) will be monitored. |
| up to 72 weeks |
| Incidence and severity of all serious adverse events (SAEs). | Incidence and severity of all serious adverse events (SAEs) during the study period (e.g., suspected unexpected serious adverse reactions, unexpected adverse device effects). | up to 72 weeks |
| Incidence of investigational product-related adverse events (AEs) leading to treatment discontinuation. | Incidence of AEs leading to discontinuation of study treatment that are related to the investigational product. | up to 72 weeks |
| Incidence of Grade 3 or higher adverse events (AEs) related to the investigational product. | Incidence of Grade 3 or higher adverse events (AEs) related to the investigational product. Systemic AEs graded per NCI-CTCAE v5.0. | up to 72 weeks |
| Levels of cellular immune responses. | Levels of cellular immune responses measured by interferon-gamma enzyme-linked immunospot (IFN-γ ELISPOT) assay in peripheral blood mononuclear cells (PBMCs) of subjects at baseline and at weeks 8, 12, 24, 48 and 72 after first dose. | Weeks 8, 12, 24, 48 and 72 |
| Levels of serum anti-GPC3 antibody titers. | Levels of serum anti-GPC3 antibody titers measured in peripheral blood samples collected at baseline and at weeks 8, 24, and 72 after initial vaccination. | Weeks 8, 12, 24, 48 and 72 |
| The Fifth Medical Center of Chinese PLA General Hospital | Not yet recruiting | Beijing | Beijing Municipality | 100071 | China |
|
| Peking Union Medical College Hospital | Not yet recruiting | Beijing | Beijing Municipality | 100730 | China |
|
| Cancer Institute and Hospital, Chinese Academy of Medical Sciences | Recruiting | Beijing | Beijing Municipality | China |
| Harbin Medical University Cancer Hospital | Not yet recruiting | Harbin | Heilongjiang | 150081 | China |
|
| Sir Run Run Shaw Hospital, Zhejiang University School of Medicine | Not yet recruiting | Hangzhou | Zhejiang | 310016 | China |
|
| D009369 | Neoplasms |
| D008113 | Liver Neoplasms |
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D004066 | Digestive System Diseases |
| D008107 | Liver Diseases |