PIN plus anti‑PD‑1 for previously treated advanced liver cancer

Treatment of Pyroptosis-inducible Newcasstle Disease Oncolytic Virus (PIN) Plus Anti-PD1 in Refractory Advanced Primary Hepatocellular Carcinoma---An Open Label Single Arm Phase I Clinical Trial.

This trial tests whether adding a new oncolytic virus called PIN to anti‑PD‑1 therapy can help people with advanced liver cancer after other treatments have stopped working.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 25 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Chinese PLA General Hospital (Academic / other)
• Drugs / interventions: immunotherapy, prednisone
• Locations: 1 site (Beijing, Biotherapeutic Department of Chinsese PLA Gereral Hospital)
• Trial ID: NCT07018518 on ClinicalTrials.gov

What this trial studies

This is a single‑center, open‑label Phase 1 trial enrolling 25–30 adults with refractory or relapsed advanced hepatocellular carcinoma to receive PIN in combination with an anti‑PD‑1 antibody. The primary focus is safety and early signs of antitumor activity, with patients monitored for adverse events and tumor responses by RECIST 1.1. The study includes translational analyses to track PIN‑induced CD8+ T cell phenotypes in peripheral blood and changes in the tumor microenvironment. Investigators will also explore immunological and clinical biomarkers that might predict toxicity or benefit.

Who should consider this trial

Good fit: Adults 18–75 years with histologically or clinically confirmed advanced or metastatic HCC, ECOG ≤2, life expectancy >3 months, refractory/relapsed after or intolerant of recommended standard therapies, and at least one measurable and injectable lesion are ideal candidates.

Not a fit: Patients with poor performance status, life expectancy under three months, no injectable lesions, or who are eligible for effective standard treatments are unlikely to benefit from this early‑phase combination.

Why it matters

Potential benefit: If successful, the combination could provoke stronger antitumor immune responses and shrink tumors, offering a new option for patients whose liver cancer progressed after standard therapies.

How similar studies have performed: Oncolytic viruses including Newcastle disease virus have shown acceptable safety and signals of activity in other cancers and preclinical data support synergy with PD‑1 blockade, but robust clinical proof in HCC remains limited.

Eligibility criteria

Inclusion Criteria:

1. Age 18-75 (inclusive).
2. Eastern Cooperative Oncology Group (ECOG) performance status ≤2 and Estimated life expectancy of more than 3 months.
3. Histopathological /cytological or diagnosed clinically confirmed locally advanced or metastatic HCC having undergone treatments recommended by the "Primary Liver CancerDiagnosis and Treatment Guidelines (2024 Edition)" ,which is refractory/relapsed after and/or intolerant of standard therapies (including targeted therapy and immunotherapy) or for which no subsequent standard therapy exists.
4. At least one measurable lesion at baseline according to investigators Response Evaluation Criteria in Solid Tumours 1.1 (RECIST 1.1).
5. Patients with injectable lesions (those suitable for direct injection or injection with the assistance of medical imaging), defined as follows: at least one injectable lesion in the skin, mucous membrane, subcutaneous tissue, lymph node or visceral organ with a longest diameter ≥10 mm.
6. Subjects are willing to accept tumor rebiopsy in the process of this study.
7. Barcelona Clinic Liver Cancer (BCLC) stage ≤C.
8. Adequate organ function as defined by the following criteria:

   * Absolute neutrophil count (ANC) ≥ 1 x 10\^9/L, Platelet count ≥50 x 10\^9/ L, hemoglobin (Hgb) ≥ 80g/L ;
   * Serum creatinine≤1.5 upper limit of normal (ULN) or creatinine clearance (as estimated by Cockcroft Gault) ≥60 mL/min;
   * Serum aspartate amino transferase (AST) and alanine aminotransferase (ALT), ≤5 x ULN ; Total serum bilirubin ≤3 x ULN);
   * Cardiac ejection fraction ≥ 50%, no evidence of pericardial effusion as determined by an echocardiogram (ECHO), and no clinically significant electrocardiogram (ECG) findings;
   * International Normalized Ratio (INR) ≤ 1.5 times the upper limit of normal (ULN), and Activated Partial Thromboplastin Time (APTT) ≤ 1.5 times ULN;
   * Baseline oxygen saturation \>91% on room air.
9. • Patients with chronic or acute hepatitis B virus (HBV) infection \[ as characterized by positive hepatitis B surface antigen (HBsAg) and/or hepatitis B core antibodies (anti-HBcAb) with detectable HBV DNA (≥20 IU/ml) \] must receive effective antiviral treatment before enrollment and during the treatment period, and their HBV DNA levels must be dynamically monitored during each treatment cycle.

   * Patients who test positive for anti-hepatitis B core (HBc) with undetectable HBV DNA (\<20 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 (≥20 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 are allowed, as long as 4 weeks have passed between completion of HCV therapy and start of study drug.
10. Previous treatments must be completed for more than 4 weeks prior to the enrollment of this study, and subjects have recovered to \<= grade 1 Toxicity (except for hematological toxicities and clinically non-significant toxicities such as alopecia).
11. Pregnancy tests for women of childbearing age shall be negative; Both men and women agreed to use effective contraception during treatment and during the subsequent 1 year.
12. Voluntarily participate in this clinical trial and sign an informed consent form.

Exclusion Criteria:

1. Subjects are being treated with either corticosteroids (\>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of enrollment.
2. Active central nervous system disease involvement (but allow patients with prior brain metastases treated at least 4 weeks prior to enrollment that are clinically stable and do not require intervention), or prior history of Common Terminology Criteria for Adverse Events (CTCAE) Grade ≥3 drug-related Central Nervous System (CNS) toxicity.
3. Presence or suspicion of fungal, bacterial, viral, or other infection that is uncontrolled or requiring intravenous (IV) antimicrobials for management.
4. Any serious underlying medical (eg, pulmonary, renal, hepatic,gastrointestinal, or neurological) or psychiatric condition or any issue that would limit compliance with study requirements.
5. Major surgery or trauma occurred within 28 days prior to enrollment, or major side effects have not been recovered.
6. Received cytotoxic chemicals, monoclonal antibodies, immunotherapy or other intervene within 4 weeks or 5 half-lives before enrollment.
7. Received radiotherapy within 3 months before enrollment.
8. Patients with primary immunodeficiency or autoimmune diseases requiring immunosuppressive therapy.
9. The presence of uncontrollable serous membrane fluid, such as massive pleural effusion or ascites.
10. Previous or concurrent cancer within 3 years prior to treatment start except for curatively treated cervical cancer in situ, non-melanoma skin cancer, superficial bladder tumors \[Ta (non-invasive tumor), Tis (carcinoma in situ) and T1 (tumor invades lamina propria)\].
11. Known positive test result for human immunodeficiency virus (HIV) or acquired immune deficiency syndrome (AIDS).
12. Prior organ allograft transplantations or allogeneic hematopoietic stem cell transplantation.
13. History of allergy or intolerance to study drug components.
14. Pregnant or breast-feeding. Women of childbearing potential must have a pregnancy test performed within 7 days before the enrollment, and a negative result must be documented.
15. Being participating any other trials or withdraw within 4 weeks.
16. Researchers believe that other reasons are not suitable for clinical trials.

Where this trial is running

Beijing, Biotherapeutic Department of Chinsese PLA Gereral Hospital

• China — Beijing, Biotherapeutic Department of Chinsese PLA Gereral Hospital, China (Recruiting)

Study contacts

• Study coordinator: Weidong Han, Ph.D

Conditions Hepatocellular Carcinoma; Adult; oncolytic viruses; PD-1