Hepatocellular CarcinomaPhase 1NCT07018518
PIN in Combination With Anti-PD1 in Previously Treated Primary Hepatocellular Carcinoma
A Phase 1 study testing PIN +anti-PD1 in people with Hepatocellular Carcinoma and Adult, run by Chinese PLA General Hospital at 1 site in China.
Trial 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) . Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Hepatocellular Carcinoma, Adult
- What is being tested?
- PIN +anti-PD1
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 1 siteChina
- Study dates
- 20 Jun 2025to 1 Dec 2030
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Show all 20Show fewer
- 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.
- 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.
- 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).
- 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.
- Voluntarily participate in this clinical trial and sign an informed consent form.
Who cannot join
- 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.
Show all 16Show fewer
- 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.
- Researchers believe that other reasons are not suitable for clinical trials.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
China
Beijing, Biotherapeutic Department of Chinsese PLA Gereral Hospital
Weidong Han, Ph.D, 010-66937231, hanwdrsw@sina.com
Yang Liu, M.D, 010-66939460, liuyang301blood@163.com
About this study
Official title: 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.
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.
Read the detailed description
Currently, systemic therapy for advanced primary HCC mainly relies on targeted therapy and immunotherapy.However,after disease progression, patients often have limited treatment options and poor prognosis.Therefore, no standard therapies beyond second-line are recommended, highlighting the urgent need for innovative treatments.
Several clinical studies have found that oncolytic viruses (OVs) can provide clinical benefits to patients with various malignant tumors, including advanced HCC.To date, there are hundreds of projects in clinical trial stages, especially in recent years, new generations of OVs developed or in clinical stages have shown better safety and stronger anti-tumor capabilities. Through genetic engineering, OVs can express target genes that have anti-tumor effects, such as granulocyte-macrophage colonystimulating factor (GM-CSF), interleukin-12(IL-12),etc, further enhancing their anti-tumor effects. Despite these advances, how to obtain a more durable antitumor immune response and long-term benefits is still an urgent clinical issue.
Previous studies have confirmed that the Newcastle disease oncolytic virus (NDV) can selectively infect tumor cells while sparing normal cells, demonstrating an acceptable safety profile. In this study, investigators have developed a nove PIN . Preclinical studies have shown that combining PIN with anti-PD1 therapy can reverse the immunosuppressive microenvironment and transform "cold" tumors into "hot" tumors, thereby triggering local and systemic anti-tumor immune responses and significantly improving the efficacy of the immune checkpoint inhibitor(ICI). Based on these preclinical findings, investigators are conducting this clinical trial to evaluate the safety and anti tumor activity of the PIN and anti-PD1 combination therapy in vivo.
In this study, 25 to 30 subjects with refractory advanced HCC will be enrolled. The initial dose for the first cycle will be determined as 4e9 or 8e9 viral particles based on the number of injectable lesions, their longest diameter, and the tumor volume capacity.
Following the first cycle of treatment, the subsequent dose and injection sites of PIN will be adjusted based on the permissible volume of the injected tumor mass, according to the following principles:
PIN injection frequency: day 0 and day 3, per 3 weeks for 8 cycles; unless unavailability of injection lesion, disease progression (PD) or serious intolerable adverse events (AEs).
PIN injection dosage:
- a.For patients with a single injectable lesion with a maximum diameter of <8 cm, the initial cycle's PIN dose is 4e9 viral particles. Subsequent cycles will maintain this dose of 4e9 or increase it to 8e9 viral particles based on the lesion's capacity to accommodate the injection volume; b. For patients with a single injectable lesion with a maximum diameter of ≥8 cm, the initial cycle's PIN dose is 8e9 viral particles. Subsequent cycles will maintain this dose of 8e9 viral particles based on the lesion's capacity to accommodate the injection volume.
- a.For patients with two injectable lesions, injections will alternate between the two lesions after two cycles. The initial cycle's PIN dose is 4e9 viral particles, and the second cycle will maintain this dose of 4e9 or increase it to 8e9 viral particles based on the tumor volume's capacity; b.For patients with injectable lesions with a maximum diameter of ≥8 cm, the initial cycle's PIN dose is 8e9 viral particles, and subsequent cycles will maintain this dose of 8e9 or decrease it to 4e9 viral particles based on the lesion's capacity.
- a.For patients with multiple injectable lesions (≥ 3), after 1-2 cycles of injections in each injectable lesion, injections are alternated between lesions. The initial injection dose for each lesion is determined by the size of the lesion; b.For lesions <3 cm, the initial cycle's dose is 4e9 viral particles, and the second cycle will maintain this dose of 4e9 or increase it to 8e9 viral particles based on the tumor volume's capacity; c.For lesions ≥3 cm, the initial cycle's injection dose is selected as 8e9 viral particles, and subsequent cycles will maintain this dose of 8e9 or decrease it to 4e9 viral particles based on the tumor volume's capacity.
- After injections, if the tumor shrinks by 0.5-1 cm in diameter, the injection dose should be adjusted to 2e9 viral particles until the tumor disappears.
Anti-PD1 infusion frequency: day -3, per 3 weeks for 8 cycles; until unacceptable toxicity occurred or PD.
Objectives:
The primary objective are to assess the safety and adverse event profile of the combination regimen.
The coprimary objective is immune response, assessed by CD8+T cells with special phenotype by Fluorescence Activating Cell Sorter (FACS). The secondary objectives are to evaluate disease control rate (DCR), objective response rate (ORR), duration of response (DOR), progression-free survival (PFS), overall survival (OS), and quality of life.
- Conditions
- Hepatocellular Carcinoma, Adult
- Being tested
- PIN +anti-PD1
- Keywords
- oncolytic viruses, PD-1
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PIN +anti-PD1Biological
- 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;
- 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.
- Salvage treatment phase: Dosage and frequency of administration refer to the initial treatment phase and maintenance treatment phase.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Biological: PIN +anti-PD1 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up to 12 months since the initiation of treatment.
Secondary outcomes (6)
DCR
DCR includes complete response (CR) ,partial response (PR) and stable disease (SD) defined by investigators according to Immune Response Evaluation Criteria in Solid Tumours (iRECIST) criteria or modified Response Evaluation Criteria in Solid Tumours (mRECIST) criteria.
Measured: Up to 2 years since the initiation of treatment.
ORR
ORR includes CR and PR defined by investigators according to iRECIST or mRECIST criteria.
Measured: Up to 2 years since the initiation of treatment.
DOR
DOR is defined as the date of their first CR or PR (which is subsequently confirmed) to PD assessed by investigators, or death regardless of cause.
Measured: Up to 5 years since the initiation of treatment.
PFS
PFS is defined as the time from the initiation of treatment to the date of PD assessed by investigators, or death any cause. Participants not meeting the criteria for progression by the analysis data cutoff date were censored at their last evaluable disease assessment date.
Measured: Up to 5 years since the initiation of treatment.
OS
OS is defined as the time from the initiation of treatment to the date of death. Subjects who have not died by the analysis data cutoff date will be censored at their last contact date.
Measured: Up to 5 years since the initiation of treatment.
Quality of Life Assessment.
Quality of life will be evaluated by European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)-Core 30 (C30) a core scale for all cancer patients, with a total of 30 items. Among them, items 29 and 30 are divided into seven levels. Based on the responses of the subjects, they are scored from 1 to 7 points. Other items are divided into four levels: never, a little, quite a bit, and a lot. When scoring, directly assign a score from 1 to 4 points.The researchers will assess changes in quality of life by calculating total scores.
Measured: Every 6 weeks up to 2 years since the initiation of treatment.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jun 2025
- Study start20 Jun 2025
- Primary completion31 Jul 2026 (estimated)
- Study completion1 Dec 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatocellular CarcinomaStudies of the same condition, open and under way.
- More trials run by Chinese PLA General HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 25 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Chinese PLA General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Changping Laboratory
- Responsible party
- Principal investigator, Han weidong, Chinese PLA General Hospital
- Investigators
- Weidong Han, Ph.D, Study director, Biotherapeutic Department, Chinese PLA General HospitalLilin Ye, Ph.D, Study director, Department of Tumor Immunology, Changping LaboratoryZhijun Wang, M.D, Study director, Department of Interventional radiology, Chinese PLA General HospitalGuanghua Rong, Ph.D, Study director, Biotherapeutic Department, the Fifth Medical Center of the PLA General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07018518
- Sponsor's protocol ID
- CHN-PLAGH-BT-096
- Status last verified
- Jun 2025
- First submitted
- 5 Jun 2025
- Last updated
- 22 Jun 2025
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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.
- ClinicalTrials.gov ID
- NCT07018518
- Acronym / sponsor ID
- CHN-PLAGH-BT-096
- Conditions
- Hepatocellular Carcinoma, Adult
- Keywords
- oncolytic viruses, PD-1
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 25 participants (estimated)
- Lead sponsor
- Chinese PLA General HospitalUniversity, hospital or other
- Collaborators
- Changping Laboratory
- Study start
- 20 Jun 2025 (actual)
- Primary completion
- 31 Jul 2026 (estimated)
- Study completion
- 1 Dec 2030 (estimated)
- First posted
- 12 Jun 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Currently, systemic therapy for advanced primary HCC mainly relies on targeted therapy and immunotherapy.However,after disease progression, patients often have limited treatment options and poor prognosis.Therefore, no standard therapies beyond second-line are recommended, highlighting the urgent need for innovative treatments.
Several clinical studies have found that oncolytic viruses (OVs) can provide clinical benefits to patients with various malignant tumors, including advanced HCC.To date, there are hundreds of projects in clinical trial stages, especially in recent years, new generations of OVs developed or in clinical stages have shown better safety and stronger anti-tumor capabilities. Through genetic engineering, OVs can express target genes that have anti-tumor effects, such as granulocyte-macrophage colonystimulating factor (GM-CSF), interleukin-12(IL-12),etc, further enhancing their anti-tumor effects. Despite these advances, how to obtain a more durable antitumor immune response and long-term benefits is still an urgent clinical issue.
Previous studies have confirmed that the Newcastle disease oncolytic virus (NDV) can selectively infect tumor cells while sparing normal cells, demonstrating an acceptable safety profile. In this study, investigators have developed a nove PIN . Preclinical studies have shown that combining PIN with anti-PD1 therapy can reverse the immunosuppressive microenvironment and transform "cold" tumors into "hot" tumors, thereby triggering local and systemic anti-tumor immune responses and significantly improving the efficacy of the immune checkpoint inhibitor(ICI). Based on these preclinical findings, investigators are conducting this clinical trial to evaluate the safety and anti tumor activity of the PIN and anti-PD1 combination therapy in vivo.
In this study, 25 to 30 subjects with refractory advanced HCC will be enrolled. The initial dose for the first cycle will be determined as 4e9 or 8e9 viral particles based on the number of injectable lesions, their longest diameter, and the tumor volume capacity.
Following the first cycle of treatment, the subsequent dose and injection sites of PIN will be adjusted based on the permissible volume of the injected tumor mass, according to the following principles:
PIN injection frequency: day 0 and day 3, per 3 weeks for 8 cycles; unless unavailability of injection lesion, disease progression (PD) or serious intolerable adverse events (AEs).
PIN injection dosage:
- a.For patients with a single injectable lesion with a maximum diameter of <8 cm, the initial cycle's PIN dose is 4e9 viral particles. Subsequent cycles will maintain this dose of 4e9 or increase it to 8e9 viral particles based on the lesion's capacity to accommodate the injection volume; b. For patients with a single injectable lesion with a maximum diameter of ≥8 cm, the initial cycle's PIN dose is 8e9 viral particles. Subsequent cycles will maintain this dose of 8e9 viral particles based on the lesion's capacity to accommodate the injection volume.
- a.For patients with two injectable lesions, injections will alternate between the two lesions after two cycles. The initial cycle's PIN dose is 4e9 viral particles, and the second cycle will maintain this dose of 4e9 or increase it to 8e9 viral particles based on the tumor volume's capacity; b.For patients with injectable lesions with a maximum diameter of ≥8 cm, the initial cycle's PIN dose is 8e9 viral particles, and subsequent cycles will maintain this dose of 8e9 or decrease it to 4e9 viral particles based on the lesion's capacity.
- a.For patients with multiple injectable lesions (≥ 3), after 1-2 cycles of injections in each injectable lesion, injections are alternated between lesions. The initial injection dose for each lesion is determined by the size of the lesion; b.For lesions <3 cm, the initial cycle's dose is 4e9 viral particles, and the second cycle will maintain this dose of 4e9 or increase it to 8e9 viral particles based on the tumor volume's capacity; c.For lesions ≥3 cm, the initial cycle's injection dose is selected as 8e9 viral particles, and subsequent cycles will maintain this dose of 8e9 or decrease it to 4e9 viral particles based on the tumor volume's capacity.
- After injections, if the tumor shrinks by 0.5-1 cm in diameter, the injection dose should be adjusted to 2e9 viral particles until the tumor disappears.
Anti-PD1 infusion frequency: day -3, per 3 weeks for 8 cycles; until unacceptable toxicity occurred or PD.
Objectives:
The primary objective are to assess the safety and adverse event profile of the combination regimen.
The coprimary objective is immune response, assessed by CD8+T cells with special phenotype by Fluorescence Activating Cell Sorter (FACS). The secondary objectives are to evaluate disease control rate (DCR), objective response rate (ORR), duration of response (DOR), progression-free survival (PFS), overall survival (OS), and quality of life.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| PIN+anti-PD1 | Experimental | Biological: PIN +anti-PD11. 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. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- 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.
Key exclusion criteria (16 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PIN +anti-PD11. 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. | Biological | PIN+anti-PD1 |
Primary outcome
Incidence of treatment-related AEs
Time frame: Up to 12 months since the initiation of treatment.
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.
6 secondary outcomes
DCR
Time frame: Up to 2 years since the initiation of treatment.
ORR
Time frame: Up to 2 years since the initiation of treatment.
DOR
Time frame: Up to 5 years since the initiation of treatment.
PFS
Time frame: Up to 5 years since the initiation of treatment.
OS
Time frame: Up to 5 years since the initiation of treatment.
Quality of Life Assessment.
Time frame: Every 6 weeks up to 2 years since the initiation of treatment.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jun 2025.
Related trials for Hepatocellular Carcinoma
RecruitingObservational study
Real-world Evaluation of the HistoSonics Edison System for Treatment of Liver Tumors Across Multidisciplinary Users (BOOMBOX: Master Study)
Liver Neoplasms, Primary Liver Cancer
Recruiting
The Vanguard Study: Testing a New Way to Screen for Cancer
Bladder Carcinoma, Breast Carcinoma
Active, not recruitingPhase 1
Prospective Exploratory Study of FAPi PET/CT With Histopathology Validation in Patients With Various Cancers
Bladder Carcinoma, Cervical Carcinoma
RecruitingObservational study
A Study to Evaluate Patient-Reported Satisfaction, Effectiveness, and Safety of Atezolizumab in Participants Treated in Routine Clinical Practice
Lung Cancer, Hepatocellular Carcinoma
RecruitingPhase 2
At-Home Cancer Directed Therapy Versus in Clinic for the Treatment of Patients With Advanced Cancer
Advanced Anal Carcinoma, Advanced Biliary Tract Carcinoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Weidong Han, Ph.D study director
Biotherapeutic Department, Chinese PLA General Hospital
Lilin Ye, Ph.D study director
Department of Tumor Immunology, Changping Laboratory
Zhijun Wang, M.D study director
Department of Interventional radiology, Chinese PLA General Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing PIN +anti-PD1 in people with Hepatocellular Carcinoma and Adult, run by Chinese PLA General Hospital at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 20 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 22 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Weidong Han, Ph.D (010-66937231 ext. +86, hanwdrsw@sina.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of treatment-related AEs (time frame: Up to 12 months since the initiation of treatment.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jun 2025.