Adoptive Autologous iNKT Cells for the Treatment of Progressed Hepatocellular Carcinoma Continuing on PD-1 Inhibitor Therapy

NCT ID: NCT05962450

Last Updated: 2024-01-16

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 84 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-10-26
• Study Completion Date: 2025-08-01

Brief Summary

The goal of this clinical trial is to explore the efficacy and safety of autologous iNKT cells in patients with progressed hepatocellular carcinoma (HCC) after treatment with PD-1 antibody. The main question it aims to answer are:

• the efficacy of autologous iNKT cells in patients with progressed HCC after treatment with PD-1 antibody.
• the safety of autologous iNKT cells in patients with progressed HCC after treatment with PD-1 antibody.

Participants will be randomized 1:1 to receive Regorafenib + PD-1 + iNKT cells (RPI group) or the treatment of Regorafenib + PD-1 (RP group).

Researchers will compare RPI group and RP group to see whether the iNKT cells can achieve a better therapeutic effect on HCC patients with PD-1 resistance.

Detailed Description

Single center, randomized, open trial in Barcelona Clinic Liver Cancer（BCLC）C stage patients with progressed HCC after anti-angiogenic targeted drugs combined with PD-1 monoclonal antibody therapy to explore the efficacy and safety of autologous iNKT cells.

This study includes screening period, treatment period and follow-up period (until the subjects withdrew their informed consent or received other anti-tumor therapy or participated in other clinical trials or the researchers judged that it is not in the best interests of patients to continue to participate in the study) after treatment.

The patients will be randomized 1:1 using a random number table to receive Regorafenib + PD-1 + iNKT cells (RPI group) or the treatment of Regorafenib + PD-1 (RP group).

1. iNKT Cells：Intravenous infusion. The cells will be infused every two weeks as a course of treatment for up to six courses.

2. PD-1：Intravenous infusion, according to the drug instructions.

3. Regorafenib：Oral administration, according to the drug instructions. All target and non-target lesions will be assessed by chest, abdomen, and pelvis CT or MRI at baseline and every 8 weeks until radiological progression (according to mRECIST/iRECIST).

Safety and side-effect profiles will be assessed based on the nature, frequency, and severity of adverse events, according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 5.0.

Conditions

Hepatocellular Carcinoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

RPI group

Regorafenib + PD-1 + iNKT cells

Group Type: EXPERIMENTAL

iNKT Cells

Intervention Type: BIOLOGICAL

the iNKT cells will be intravenous infused every two weeks as a course of treatment for up to six courses , the reinfusion dose is determined according to the patient's body surface area, which was about 108\~109cells/m2.

PD-1

Intervention Type: DRUG

Intravenous infusion, according to the drug instructions.

Regorafenib

Intervention Type: DRUG

Oral administration, according to the drug instructions.

RP group

Regorafenib + PD-1

Group Type: OTHER

PD-1

Intervention Type: DRUG

Intravenous infusion, according to the drug instructions.

Regorafenib

Intervention Type: DRUG

Oral administration, according to the drug instructions.

Interventions

iNKT Cells

the iNKT cells will be intravenous infused every two weeks as a course of treatment for up to six courses , the reinfusion dose is determined according to the patient's body surface area, which was about 108\~109cells/m2.

Intervention Type: BIOLOGICAL

PD-1

Intravenous infusion, according to the drug instructions.

Intervention Type: DRUG

Regorafenib

Oral administration, according to the drug instructions.

Intervention Type: DRUG

Other Intervention Names

Vα24+ T Cells

Eligibility Criteria

Inclusion Criteria

• 18-75 years of age.
• Barcelona Clinic Liver Cancer（BCLC） C stage hepatocellular carcinoma (HCC) confirmed by CT, MRI, and/or histopathology.
• Progressed after receiving anti-angiogenic targeted drugs combined with PD-1 monoclonal antibody.
• Life expectancy of at least 12 weeks.
• Child-Pugh A/B.
• Voluntary signing of informed consent.

Exclusion Criteria

• History of severe hypertension or cardiac disease.
• known central nervous system (CNS) tumor or combined with other malignant disorders.
• Uncontrolled immune system or infectious disease.
• Known history of the human immunodeficiency virus (HIV) or syphilis infection.
• History of stem cell transplant or organ allograft.
• History of allergy to immunotherapy or related drugs.
• Bilirubin is twice times the upper limit of normal.
• Glomerular filtration rate （GFR）< 60ml/min.
• Serious complications include moderate or severe infective pleural and peritoneal effusion, pericardial effusion, upper gastrointestinal bleeding, hepatic encephalopathy.
• Pregnancy or lactation.
• History of severe allergy to any monoclonal antibody or anti-angiogenic targeted drug.
• Deemed not suitable for cellular immunotherapy by the investigators.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Beijing Gene Key Life Technology Co., Ltd

INDUSTRY

Sponsor Role: collaborator

Beijing YouAn Hospital

OTHER

Sponsor Role: lead

Responsible Party

LU JUN

Chief physician

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jun Lu, MD.

Role: PRINCIPAL_INVESTIGATOR

Beijing YouAn Hospital

Locations

Beijing Youan Hospital,Capital Medical University

Beijing, Beijing Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

Jun Lu, MD.

Role: CONTACT

lujun98@ccmu.edu.cn

86-13661381489

Songtao Liu, MD.

Role: CONTACT

botao8080@163.com

86-13811120755

Facility Contacts

Songtao Liu, MD.

Role: primary

botao8080@163.com

86-13811120755

Other Identifiers

Beijing YouAn Ethics [2023]060

Identifier Type: -

Identifier Source: org_study_id