PIN in Combination With Anti-PD1 in Previously Treated Primary Hepatocellular Carcinoma

NCT07018518 | Recruiting Phase 1

• 1 other identifier: CHN-PLAGH-BT-096
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

In this single-center,open-label, phase I study, the safety and efficacy of PIN in combination with programmed cell death protein antibody (anti-PD1) therapeutic regimen will be evaluated in patients with refractory primary advanced hepatocellular carcinoma(HCC) . A total of 25 to 30 patients are planned to be enrolled and receive PIN plus anti-PD1 combined treatment. It aims to: 1).assess the safety and antitumor effects of the above combined treatment regimen. 2).detect the dynamic changes and molecular characteristics of PIN-induced CD8+ T cells with special phenotype in peripheral blood (PB) and transformation of tumor microenvironment (TME) after the treatment with PIN. 3).evaluate the immunological or clinical predictive biomarkers for toxicity and efficacy.

Conditions

Hepatocellular Carcinoma; Adult

Keywords

oncolytic viruses; PD-1

Outcome Measures

Primary Outcomes (1)

• Incidence of treatment-related AEs

  Treatment-related AEs are defined as any adverse medical events occurring since the initiation of treatment and grading these toxicities by Common Terminology Criteria for Adverse Events (CTCAE) V5.0.

  Up to 12 months since the initiation of treatment.

Secondary Outcomes (6)

• DCR

  Up to 2 years since the initiation of treatment.

• ORR

  Up to 2 years since the initiation of treatment.

• DOR

  Up to 5 years since the initiation of treatment.

• PFS

  Up to 5 years since the initiation of treatment.

• OS

  Up to 5 years since the initiation of treatment.

Other Outcomes (2)

• Immunological response

  PB samples are collected at least on day 0 (before PIN injection), 2, 3 (before PIN injection) and 5 during each treatment cycle ( each cycle is 21 days).

• The level of cytokines and anti-PIN antibodies in serum .

  PB samples are collected at least on day 0 (before PIN injection), 2, 3 (before PIN injection) and 5 during each treatment cycle ( each cycle is 21 days).

Study Arms (1)

PIN+anti-PD1

EXPERIMENTAL

1. Initial treatment phase: The combined treatment of PIN and anti-PD1 will be administered for 8 cycles; Unless PD or serious intolerable AEs. 2. Maintenance treatment phase: For patients who completed 8 cycles treatment and obtained effective disease control, if residual tumor lesions are still accessible for local injection, combination therapy will be continued. If no injectable lesion, anti-PD1 will be administrated per 3 weeks till 2 years unless PD or serious intolerable AEs. 3. Salvage treatment phase: For patients who experience disease recurrence or progression 16 weeks after ceasing PIN injection, if there are accessible lesions available for PIN injection, combination therapy will be resumed. If specific T cells induced by PIN can be detected in PB when there is no injectable lesion, then the specific T cells are amplified and transfused for salvage therapy.

Biological: PIN +anti-PD1

Interventions

PIN +anti-PD1 BIOLOGICAL

1. Initial treatment phase: PIN injection frequency: day 0 and day 3, per 3 weeks for 8 cycles; PIN injection dosage: Cycle1: 4e9 or 8e9 viral particles of PIN based on the number of injectable lesions, their longest diameter, and the tumor volume capacity . Cycle 2\~8: 4e9 or 8e9 viral particles of PIN based on the tumor volume's capacity. Anti-PD1: day -3, per 3 weeks for 8 cycles; 2. Maintenance treatment phase: No injection lesion: Anti-PD1: day 1, per 3 weeks till 2 years unless PD or serious intolerable AEs. Have injection lesion: PIN: 4e9 or 8e9 viral particles based on the tumor volume's capacity, per 6 weeks (within first 24 weeks), then per 8 weeks till 2 years unless unavailability of injection lesion, PD or serious intolerable AEs. Anti-PD1: day 1, per 3 weeks till 2 years unless PD or serious intolerable AEs. 3. Salvage treatment phase: Dosage and frequency of administration refer to the initial treatment phase and maintenance treatment phase.

PIN+anti-PD1

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18-75 (inclusive).
• Eastern Cooperative Oncology Group (ECOG) performance status ≤2 and Estimated life expectancy of more than 3 months.
• 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.
• At least one measurable lesion at baseline according to investigators Response Evaluation Criteria in Solid Tumours 1.1 (RECIST 1.1).
• 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.
• Subjects are willing to accept tumor rebiopsy in the process of this study.
• Barcelona Clinic Liver Cancer (BCLC) stage ≤C.
• 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.
• 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.

You may not qualify if:

• Subjects are being treated with either corticosteroids (\>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of enrollment.
• 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.
• Presence or suspicion of fungal, bacterial, viral, or other infection that is uncontrolled or requiring intravenous (IV) antimicrobials for management.
• Any serious underlying medical (eg, pulmonary, renal, hepatic,gastrointestinal, or neurological) or psychiatric condition or any issue that would limit compliance with study requirements.
• Major surgery or trauma occurred within 28 days prior to enrollment, or major side effects have not been recovered.
• Received cytotoxic chemicals, monoclonal antibodies, immunotherapy or other intervene within 4 weeks or 5 half-lives before enrollment.
• Received radiotherapy within 3 months before enrollment.
• Patients with primary immunodeficiency or autoimmune diseases requiring immunosuppressive therapy.
• The presence of uncontrollable serous membrane fluid, such as massive pleural effusion or ascites.
• 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 \[Ta (non-invasive tumor), Tis (carcinoma in situ) and T1 (tumor invades lamina propria)\].
• Known positive test result for human immunodeficiency virus (HIV) or acquired immune deficiency syndrome (AIDS).
• Prior organ allograft transplantations or allogeneic hematopoietic stem cell transplantation.
• History of allergy or intolerance to study drug components.
• 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.
• Being participating any other trials or withdraw within 4 weeks.

Sponsors & Collaborators

• Chinese PLA General Hospital: lead
• Changping Laboratory: collaborator

Study Sites (1)

China

Beijing, Biotherapeutic Department of Chinsese PLA Gereral Hospital, China

RECRUITING

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Study Officials

• Weidong Han, Ph.D

  Biotherapeutic Department, Chinese PLA General Hospital

  STUDY DIRECTOR

• Lilin Ye, Ph.D

  Department of Tumor Immunology, Changping Laboratory

  STUDY DIRECTOR

• Zhijun Wang, M.D

  Department of Interventional radiology, Chinese PLA General Hospital

  STUDY DIRECTOR

• Guanghua Rong, Ph.D

  Biotherapeutic Department, the Fifth Medical Center of the PLA General Hospital

  STUDY DIRECTOR

Central Study Contacts

Weidong Han, Ph.D

CONTACT

010-66937231; hanwdrsw@sina.com

Yang Liu, M.D

CONTACT

010-66937463; liuyang301blood@163.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Biotherapeutic Department

Study Record Dates

• First Submitted: June 5, 2025
• First Posted: June 12, 2025
• Study Start: June 20, 2025
• Primary Completion (Estimated): July 31, 2026
• Study Completion (Estimated): December 1, 2030
• Last Updated: June 22, 2025

Record last verified: 2025-06

Locations

CN (1)