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

Liver Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05123209
• Other study ID #: YMCART202101
• Status: Recruiting
• Phase: Phase 1
• Start date: August 24, 2021
• Est. completion date: August 30, 2023

Study information

• Verified date: September 2021
• Source: Beijing Immunochina Medical Science & Technology Co., Ltd.
• Contact: Fei Wu, MD
• Phone: +8615801390058
• Email: wufei[@]immunochina.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 12
• Est. completion date: August 30, 2023
• Est. primary completion date: August 30, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Liver Cancer
• Liver Neoplasms

Intervention

Biological:
• IM83 CAR-T cells
3×10^9 CAR-T cells

Combination Product:
• The second-line treatment of liver cancer
approved by NMPA

Locations

Country	Name	City	State
China	Chinese PLA GENERAL HOSPITAL	Beijing	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Beijing Immunochina Medical Science & Technology Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Plasma levels of a fetoprotein (AFP) cells infusion		At 28 days, 3 months and 6 months after CAR-T cell infusion
Secondary	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