Resumen

Elegibilidad

Detalles del diseño

Brazos e Intervenciones

Medidas de resultado

Sitios del ensayo

Fuente: NCT07018518

Reclutando

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

Intervencionista

Fase 1

China

Patrocinador: Chinese PLA General Hospital

Última actualización: 22 de junio de 2025
Aviso: La información proviene de registros públicos y puede no reflejar cambios en tiempo real en el centro local.

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.

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Categoría de tratamiento

Terapia dirigida

Erforderliche Mutationen

Ninguna

Ensayo iniciado

20 de junio de 2025

Última actualización por el patrocinador

22 de junio de 2025

Finalización estimada

31 de julio de 2026

Contacto del estudio

Nombre:Weidong Han, Ph.D

Correo electrónico:hanwdrsw@sina.com

Teléfono:010-66937231

Nombre:Yang Liu, M.D

Correo electrónico:liuyang301blood@163.com

Teléfono:010-66937463

Elegibilidad

Criterios de inclusión

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.

Criterios de exclusión

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.

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Detalles del diseño

AsignaciónN/A

Modelo de intervenciónSingle Group Assignment

EnmascaramientoNone (Open Label)

Número a inscribir25

Brazos e Intervenciones

Brazos

Intervenciones

Tipo: Experimental

Descripción: 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.

Intervenciones:

PIN +anti-PD1

Medidas de resultado

Medidas de resultado primarias

Incidence of treatment-related AEsUp 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.

Medidas de resultado secundarias

DORUp to 5 years since the initiation of treatment.

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.

PFSUp to 5 years since the initiation of treatment.

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.

OSUp to 5 years since the initiation of treatment.

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.

DCRUp to 2 years since the initiation of treatment.

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.

ORRUp to 2 years since the initiation of treatment.

ORR includes CR and PR defined by investigators according to iRECIST or mRECIST criteria.

Quality of Life Assessment.Every 6 weeks up to 2 years since the initiation of treatment.

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.

Immunological responsePB 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).

Dynamics and molecular characteristics of CD8+ T cells with special phenotypes induced by PIN injection and its association with the treatment outcome. The relationship between the number of the CD8+ T cells and its anti-tumor effect was analyzed. To analyze the number and function of the CD8+ T cells in PB of patients with primary or acquired resistance after PIN injection and to summarize the key cellular and molecular mechanisms of resistance.

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).

The cytokines mainly include interleukin-1beta (IL-1β ) (pg / ml), IL-2(U/ml), IL-6(pg / ml),IL-10(pg / ml), tumor necrosis factor-α (TNF-α)(pg / ml), et al.

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Sitios del ensayo

Este estudio tiene 1 sitio de ensayo

China

Beijing, Biotherapeutic Department Of Chinsese PLA Gereral Hospital, CN

Nombre:Yang Liu, M.D

Correo electrónico:liuyang301blood@163.com

Teléfono:010-66939460

Reclutando

Beijing, Biotherapeutic Department Of Chinsese PLA Gereral Hospital, CN

China

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