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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
84
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.
Intravenous infusion, according to the drug instructions.
Oral administration, according to the drug instructions.
Beijing Youan Hospital,Capital Medical University
Beijing, Beijing Municipality, China
RECRUITINGProgression-Free Survival (PFS)
The time from enrollment to disease progression according to the modified RECIST (mRECIST) guideline in trial immunotherapeutics, or death from any cause, whichever occurred first；the time from enrollment to confirmed disease progression (iCPD) according to the iRECIST
Time frame: The time from enrollment to disease progression, or death from any cause, whichever occurred first, up to 24 months.
Disease control rate (DCR)
including complete response (CR), partial response (PR), and disease stabilization (SD), evaluated by imaging according to iRECIST for target lesions and assessed by MRI/CT.
Time frame: Evaluation was performed every 8 weeks after the start of the treatment, up to 24 months.
Objective response rate (ORR)
complete response (CR) and partial response (PR) evaluated by imaging according to mRECIST/iRECIST for target lesions and assessed by MRI/CT.
Time frame: Evaluation was performed every 8 weeks after the start of the treatment, up to 24 months.
Overall survival (OS)
Time from the date of enrollment to the date of death from any cause.
Time frame: Time from the date of enrollment to the date of death from any cause, up to 36 months.
1-year overall survival rate (1-year OS rate)
The proportion of subjects who were still alive from the date of enrollment to 1 year later
Time frame: Time from the date of enrollment to 1 year later.
Duration of Overall Response (DOR)
The time from the first tumor remission (CR or PR according to mRECIST/iRECIST) to the first recording of disease progression (PD according to mRECIST criteria or iCPD according to iRECIST) or death from any cause (whichever occurs first).
Time frame: Time from the first tumor remission to the first recording of disease progression or death from any cause, up to 24 months..
Time to progression (TTP)
Time from the date of enrollment to the date of first disease progression (PD) according to mRECIST or iCPD according to iRECIST).
Time frame: Time from the date of enrollment to the date of first disease progression, up to 24 months.
Time to Quality of Life (QoL) Deterioration
EORTC QLQ-C30: European Organization for Research on Treatment of Cancer Quality of Life Questionnare-Core 30. The totally 30 items spread out over five functional scales (15 items), three symptom scales (7 items), a global health status/QoL scale (2 items), and six single items. 1-28 item ranges 1: not at all, 2: a little, 3: quite a lit, 4: very much; 29-30 item ranges 1-7 from very poor to excellent. Raw score (RS) is an average of all items in each area. Standardized score is in the range of 0-100 by formula SS=\[1-(RS-1)/n\] x100 (function) or SS=\[（RS-1）/n\]x100 (symptom or overall health) respectively. A high scale score represents a higher/healthy response level. Time to deterioration was defined as a decrease from baseline of 10 points or more on the EORTC QLQ-C30 maintained for two consecutive assessments.
Time frame: Time from the date of enrollment, up to 24 months.
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