B010-A Injection for Treating Patients With GPC3 Positive Advanced Hepatocellular Carcinoma

NCT05070156 | Unknown Early Phase 1 DMC

• 1 other identifier: B010-A-001
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

This is an Open-label, Single Arm study to observe the safety and tolerability of B010-A in the treatment of advanced hepatocellular carcinoma.

Conditions

Advanced Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (1)

• Evaluate incidence of treatment-emergent adverse events [Safety and Tolerability] after B010-A injection.

  Up to 24 months post B010-A injection.

Secondary Outcomes (11)

• Evaluate the cellular kinetics of subjects after B010-A injection.

  Up to 24 months post B010-A injection.

• Evaluate the cellular kinetics of subjects after B010-A injection.

  Up to 24 months post B010-A injection.

• Evaluate the pharmacodynamics of subjects after B010-A injection.

  Up to 24 months post B010-A injection.

• Evaluate the pharmacodynamics of subjects after B010-A injection.

  Up to 24 months post B010-A injection.

• Evaluate the preliminary efficacy of B010-A after injection.

  Up to 24 months post B010-A injection.

Study Arms (1)

Experimental: B010-A injection for patient with GPC3 Positive Hepatocellular Carcinoma

EXPERIMENTAL

Biological: Biological/Vaccine: Low-dose group; Biological: Biological/Vaccine: Mid-dose group; Biological: Biological/Vaccine: High-dose group

Interventions

Biological/Vaccine: Low-dose group BIOLOGICAL

1.0×105/kg positive CAR-T cells injection. 2-n doses will be evaluated by the investigator if participant is qualify for certain condition.

Experimental: B010-A injection for patient with GPC3 Positive Hepatocellular Carcinoma

Biological/Vaccine: Mid-dose group BIOLOGICAL

2.0×105/kg positive CAR-T cells injection. 2-n doses will be evaluated by the investigator if participant is qualify for certain condition.

Experimental: B010-A injection for patient with GPC3 Positive Hepatocellular Carcinoma

Biological/Vaccine: High-dose group BIOLOGICAL

3.0×105/kg positive CAR-T cells injection. 2-n doses will be evaluated by the investigator if participant is qualify for certain condition.

Experimental: B010-A injection for patient with GPC3 Positive Hepatocellular Carcinoma

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All subjects must meet all of the following criteria to be eligible for enrollment in this study:
• Aged 18-75 years, male or female;
• Subjects with histopathologically or cytologically confirmed advanced hepatocellular carcinoma (HCC) who are ineligible for surgery or local therapy, have progressed or being intolerant to prior standard systemic therapies (systemic therapies include but are not limited to systemic chemotherapy and molecular targeted therapy), or those who have no effective treatment options at the time of enrollment as judged by the investigator;
• Subjects with at least one stable and evaluable intrahepatic or extrahepatic target lesion (longest diameter of non-nodal lesions ≥ 10 mm, or short axis of lymph node lesions ≥ 15 mm) at enrollment as per RECIST V1.1 criteria;
• Subjects with GPC3 positive (\> grade 2) tumor tissue samples (\> 25% tumor cells positive staining) as tested by immunohistochemistry (IHC);
• Subjects with Barcelona Clinic Liver Cancer Stage C (BCLC-C) hepatocellular carcinoma, or subjects with BCLC Stage B hepatocellular carcinoma who are not amenable to local therapy or have progressed after local therapy;
• Subjects with expected survival \> 12 weeks;
• Subjects with liver cirrhosis of Child-Pugh grade A (5-6 points);
• Subjects with Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;
• Subjects with inactive hepatitis B (if HBsAg or HBcAb is positive, then HBV-DNA must be \< 20 IU/mL, and HBsAg-positive patients should have been treated with antiviral therapies as per the Guidelines for the Prevention and Treatment of Chronic Hepatitis B (2019 Edition));
• The largest diameter of intrahepatic tumors is \< 10 cm, and the number of multiple tumors is \< 10 (if pulmonary metastatic lesions are present, the number of metastatic lesions is \< 6);
• Subjects with a venous access for mononuclear cell collection;
• Subjects with adequate bone marrow function that allows for lympho-depleting pre-conditioning and without contraindications for the pre-conditioning as assessed by the investigator;
• Subjects with liver, kidney, respiratory, cardiovascular functions, and corresponding hematological levels as defined below:
• Alanine aminotransferase (ALT) ≤ 5.0 × ULN, aspartate aminotransferase (AST) ≤ 5.0 × ULN, and total bilirubin ≤ 2.5 × ULN at screening;

You may not qualify if:

• Subjects who meet any of the following criteria cannot participate in this study:
• Having other uncured malignancies (except cervical carcinoma in situ and basal cell carcinoma of skin) within the past 5 years or at present, or hepatocellular carcinoma with brain metastases;
• With a history of any of the following cardiovascular diseases within the past 6 months: New York Heart Association (NYHA) Grade III or IV heart failure, cardiac angioplasty or stenting, myocardial infarction, unstable angina, or other clinically significant heart diseases, or poorly controlled high blood pressure (systolic blood pressure \> 150 mm Hg, or diastolic blood pressure \> 90 mm Hg), or hypotension that requires treatment with vasopressors;
• With metastases to the central nervous system (CNS) and clinically significant CNS disorders; with prior or clinically significant CNS diseases at screening, such as epilepsy, seizures, paralysis, aphasia, stroke, severe brain injury, dementia, Parkinson's disease, cerebellar disease, brain organic syndrome or psychiatric disorder;
• With prior hepatic encephalopathy or at present;
• With a history of serious lung diseases, including pulmonary embolism, chronic obstructive pulmonary disease, interstitial lung disease and clinically significant abnormal findings in pulmonary function tests;
• With an active infection (uncontrolled active infections caused by bacteria, viruses, or fungus requiring systemic therapy) at screening, or has an unexplained fever of ≥ 38.0 °C during screening or prior to the first dose;
• With known active autoimmune diseases requiring immunosuppressive therapy, including biologics;
• With a history of organ transplantation or awaiting organ transplantation (including liver transplantation);
• With ≥ 50% of liver replaced by tumor, or with the main portal vein tumor thrombus, or the mesenteric vein/inferior vena cava has been invaded by tumor thrombus;
• With a co-infection of HBV and HCV viruses or infections caused by more than two viruses;
• Positive HCV-RNA, HIV antibody, or syphilis serology, or any other uncontrollable active infections;
• Requiring long-term antiplatelet therapy (aspirin \> 300 mg/day; clopidogrel \> 75 mg/day);
• Have received prior cell-based therapies such as targeted GPC3 therapy, TCR-T therapy, CAR-T therapy;
• With moderate or higher amount of pleural effusion/ascites with clinical symptoms, or have undergone drainage of pleural effusion/ascites within the past month (except for those with only small amounts of pleural effusion/ascites revealed by imaging examinations but without symptoms);

Sponsors & Collaborators

• Tongji University: lead
• Shanghai Pharmaceuticals Holding Co., Ltd: collaborator

Study Sites (1)

Shanghai Tenth People's Hospital

Shanghai, Shanghai Municipality, 200072, China

Location

MeSH Terms

Interventions

Biological Products; Vaccines; Population Groups

Intervention Hierarchy (Ancestors)

Complex Mixtures; Demography; Population Characteristics

Study Officials

• Qing Xu

  Shanghai 10th People's Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principle Investigator

Study Record Dates

• First Submitted: September 10, 2021
• First Posted: October 7, 2021
• Study Start: October 29, 2021
• Primary Completion: August 31, 2024
• Study Completion: September 30, 2024
• Last Updated: December 15, 2023

Record last verified: 2023-12

Locations

CN (1)