Safety and Efficacy Evaluation of IM83 CAR-T Cells for Patients With Advanced Liver Tumors

Safety and Efficacy Evaluation of IM83 CAR-T Cells for Patients Wirh Advanced Liver Tumors

This is a open-label, single center, cohort study to determine the efficacy and safety of IM83 CAR-T cells in patients with advanced Liver Tumors.

Study Overview

• Status: Recruiting
• Conditions: Liver Cancer
• Intervention / Treatment: Biological: IM83 CAR-T cells; Combination product: The second-line treatment of liver cancer

• Study Type: Interventional
• Enrollment (Anticipated): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100039
      • Recruiting
      • Chinese PLA General Hospital
      • Contact: Jianming Xu, M.D.; Phone Number: +8613910866712; Email: Jianmingxu2014@163.com
      • Principal Investigator: Jianming Xu, M.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• ≥ 18 years old, male or female.
• Patients with advanced hepatocellular carcinoma (HCC) diagnosed by histopathology or cytology, Barcelona stage B-C.
• Progression or intolerance after receiving standardized systematic treatment in the past (at least first-line treatment fails, and PD-1 / PD-L1 drugs can be used).
• Patients in car-t combined treatment group need to have not received the combined drugs before.
• At least one measurable target lesion according to RECIST1.1.
• Tumor cells expressed GPC3 antigen.
• Child Pugh score of liver function ≤ 7.
• ECOG 0-1.
• Estimated survival ≥ 12 weeks;
• Laboratory inspection shall at least meet the following specified indicators:

ANC≥ 1.5 × 10 ^ 9 / L，platelet ≥ 75 × 10 ^ 9 / L ，Hemoglobin ≥ 90 g / L，Serum creatinine ≤ 1.5 ULN，serum bilirubin ≤ 3 ULN，INR≤ 2，AST and ALT)≤ 5.0 ULN，Creatinine clearance rate ≥ 60 ml / min.

• The left ventricular ejection fraction was > 50%.

Exclusion Criteria:

• The researcher has determined that the subject has autoimmune diseases that are not suitable to participate in this study, such as systemic lupus erythematosus, rheumatoid arthritis, ulcerative colitis.
• History of epilepsy or other central nervous system diseases that may affect the test in the judgment of the investigator.
• The washout period of chemotherapy, molecular targeted therapy, immunotherapy, hepatic artery chemoembolization, radiofrequency ablation, radiotherapy for non target lesions or other anti-tumor drugs within 1 week before blood collection is less than 5 half lives.
• Systemic glucocorticoids (local use is allowed) or other immunosuppressants were used within 3 days before apheresis.
• Other incurable malignant tumors in the past 5 years or at the same time, except cervical carcinoma in situ, skin basal cell carcinoma and breast ductal carcinoma in situ.
• The investigator assessed that the subject had poorly controlled pleural effusion, ascites or pericardial effusion.
• Hypertension with poor drug control (systolic blood pressure > 160mmhg and / or diastolic blood pressure > 90mmHg) or cardiovascular and cerebrovascular diseases with clinical significance (such as active) within 6 months before signing the informed consent, such as cerebrovascular accident, myocardial infarction, unstable angina pectoris, or severe arrhythmia, which cannot be controlled by drugs or has potential impact on the study treatment.
• Combined with other serious organic diseases or mental diseases.
• Subjects with HBsAg or HBcAbpositive and peripheral blood HBV DNA titers of >2000 IU/ml (HBsAg positive but HBV DNA titer <2000 IU/ml of peripheral blood and eligible for antiviral treatment according to chronic hepatitis B prevention guideline 2019 Edition). HCV antibody positive and HCV RNA in peripheral blood > 500 IU / ml. Syphilis antibody positive.
• Male subjects who are pregnant or breastfeeding during the screening period, or who plan pregnancy during treatment or within 1 year after the end of treatment, or whose partner plans pregnancy within 1 year after the end of treatment.
• There were active or uncontrollable infections requiring systemic treatment within 1 week before cell apheresis.
• Other researchers believe that it is not suitable for inclusion.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: IM83 CAR-T cells	Biological: IM83 CAR-T cells; 3×10^9 CAR-T cells
Experimental: IM83 CAR-T cells +The second-line treatment	Biological: IM83 CAR-T cells; 3×10^9 CAR-T cells; Combination product: The second-line treatment of liver cancer; approved by NMPA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence of adverse events (AEs) and abnormal laboratory test results as assessed by CTCAE V5.0	Up to 28 days after CAR-T cell infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate (ORR)	ORR, defined as the proportion of participants with a complete response or partial response, as determined by the investigator according to RECIST v1.1	At 28 days, 3 months and 6 months after CAR-T cell infusion
Duration of Response (DOR)	DOR, defined as the time from the first occurrence of a documented objective response to disease progression or death from any cause (whichever occurs first) in Stage 1, as determined by the investigator according to RECIST v1.1	Up to 24 weeks after CAR-T cell infusion
Progression-free survival (PFS)	PFS, defined as the time from CAR-T cell infusion to the first occurrence of disease progression or death from any cause (whichever occurs first) , as determined by the investigator according to RECIST v1.1	Up to 24 weeks after CAR-T cell infusion
Overall survival (OS)	OS , defined as the time from CAR-T cell infusion to death from any cause	Up to 24 weeks after CAR-T cell infusion
Plasma levels of α fetoprotein (AFP) cells infusion		At 28 days, 3 months and 6 months after CAR-T cell infusion
Persistence of CAR-T cells (cell counts and cell percentage in peripheral blood)	The persistence over time of CAR T cells in the peripheral blood as determined by flow cytometry and qPCR.	Up to 24 weeks after CAR-T cell infusion

Collaborators and Investigators

• Sponsor: Beijing Immunochina Medical Science & Technology Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): August 24, 2021
• Primary Completion (Anticipated): August 30, 2023
• Study Completion (Anticipated): August 30, 2023

Study Registration Dates

• First Submitted: September 8, 2021
• First Submitted That Met QC Criteria: November 5, 2021
• First Posted (Actual): November 17, 2021

Study Record Updates

• Last Update Posted (Actual): November 17, 2021
• Last Update Submitted That Met QC Criteria: November 5, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms
• Other Study ID Numbers: YMCART202101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No