Hepatocellular carcinoma
Conditions
Interventions
Group1:SynOV1.1 Adenovirus Injection + Molecular Targeted Agents
Group2:SynOV1.1 Adenovirus Injection + Anti-PD-1/CTLA-4 Antibodies
Sponsors
The Fifth Medical Center of Chinese PLA General Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 80 Years
Inclusion criteria
Inclusion criteria: 1.Voluntarily participates in the clinical study; fully understands and is informed about the study; willing and able to comply with and complete all trial procedures. 2.Aged 18 to 80 years (inclusive). 3.Clinically diagnosed with unresectable, advanced primary hepatocellular carcinoma (HCC) meeting all of:AFP-positive (AFP > 20 µg/L);Primary resistance: Failure of standard targeted-immunotherapy (anti-angiogenic agents, TKIs, and/or PD-1 immune checkpoint inhibitors); Initial response followed by progression on standard therapy. 4.At least one non-resectable lesion suitable for direct intratumoral injection or image-guided real-time injection, with:Longest diameter >= 10 mm and = 12 weeks. 7.Adequate Organ Function :Hematologic Absolute Neutrophil Count (ANC) >= 1.5×10^9/L Platelets (PLT) >= 60×10^9/L Hemoglobin (Hb) >= 90 g/L Liver Total Bilirubin (TBIL) = 2.8 g/dL Renal Creatinine = 50 mL/min (Cockcroft-Gault) Coagulation Activated Partial Thromboplastin Time (aPTT) = 90 days after last dose.
Exclusion criteria
Exclusion criteria: 1.Received any systemic antitumor therapy within 4 weeks prior to the first study drug administration, including chemotherapy, biotherapy, hormonal therapy, or radiotherapy. Exceptions:Molecular targeted agents (lenvatinib/regorafenib) in combination groups need not be discontinued.Anti-PD-1/CTLA-4 antibodies in combination groups need not be discontinued.Underwent local therapy or surgery for target lesions (e.g., ethanol injection, RFA, TACE, HAIC) within 4 weeks. 2.Received systemic corticosteroids (>10 mg prednisone/day or equivalent) or immunosuppressants within 14 days prior. Exclusions:Topical/ocular/intra-articular/intranasal/inhaled corticosteroids.Short-term prophylactic corticosteroids (e.g., contrast allergy prevention). 3.Used immunomodulatory drugs (e.g., thymosin, IL-2, interferon) within 14 days prior. 4.Administered live attenuated vaccines (e.g., measles, mumps, rubella, varicella/zoster, yellow fever, rabies, BCG, typhoid) within 4 weeks prior. Note:Inactivated vaccines (e.g., injectable seasonal influenza) permitted.Live intranasal influenza vaccines prohibited. 5.Prior treatment with oncolytic viruses or gene therapies. 6.Received any investigational drug within 4 weeks prior. 7.Concurrent enrollment in another interventional clinical trial (excluding observational studies or follow-up phases). 8.Major surgery (excluding needle biopsy) or significant trauma within 4 weeks prior, or planned elective surgery during the trial. 9.Persistent toxicities from prior antitumor therapy > Grade 1 per NCI-CTCAE v5.0 (excluding alopecia or investigator-determined low-risk toxicities). 10.Active/symptomatic CNS metastases or leptomeningeal disease, unless:Treated brain metastases with stable disease (no progression >= 4 weeks) AND no steroid use within 7 days prior.All patients with suspected CNS symptoms require baseline CT/MRI. 11.History of leptomeningeal disease. 12.Uncontrolled comorbidities affecting compliance (e.g., severe portal hypertension requiring intervention, hepatic encephalopathy, SVC syndrome). 13.Significant cardiovascular disease, including:Severe arrhythmias requiring intervention (e.g., ventricular arrhythmia, AV block II-III, QTc >= 480 ms).Acute coronary syndrome, MI, CHF, stroke (Grade >= 3) within 6 months prior.NYHA Class >= II or LVEF 50% liver volume, IVC invasion.Tumors adjacent to critical neurovascular structures/airways.High-risk locations for intratumoral injection.Contraindications to contrast-enhanced CT/MRI. 20.Significant bleeding events within 1 month prior increasing injection risk. 21.Inability to discontinue anticoagulants/antiplatelets: Drug Washout Period Aspirin >= 7 days prior Warfarin >= 7 days prior LMWH >24 hours prior UFH >4 hours prior DOACs (dabigatran, rivaroxaban, etc.) >= 4 days prior 22.Active infection requiring systemic therapy. 23.Severe active inflammatory skin disease or history of severe eczema requiring medication. 24.Prior or p
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| ORR; | — |
Secondary
| Measure | Time frame |
|---|---|
| DOR;DCR;PFS;OS; | — |
Countries
China
Contacts
Public Contactluyinying
The Fifth Medical Center of Chinese PLA General Hospital
Outcome results
None listed