GPC3-directed CAR-T in the Treatment Amongst Subjects With Advanced Hepatocellular Carcinoma

Official title

JWATM214，an Armored GPC3-directed CAR-T ，in the Treatment Amongst Subjects With Advanced Hepatocellular Carcinoma ：a Single-arm, Open-label，Dose-escalation Study

Overview

This is a single arm, open-label, dose escalation clinical study to evaluate the safety and efficacy of infused autologous armored GPC3-directed CAR-T in patients with advanced hepatocellular carcinoma refractory to prior systematic treatments.

Interventions

• Biological CAR-GPC3 T cells
  Subjects will undergo leukapheresis to isolate peripheral blood mononuclear cells (PBMCs) for the production of JWATM214 . During JWATM214 production, subjects will receive a preconditioning chemotherapy regimen of cyclophosphamide and fludarabine to deplete the lymphocytes. After lymphodepletion, subjects will receive single-dose treatment with JWATM214 by intravenous (IV) injection.

Primary outcome measures

• Treatment-related adverse events (AEs) [Time frame: 2 years]
• Dose-limiting toxicities [Time frame: 28 days]
• RP2D of JWATM214 in HCC patients [Time frame: 2 years]

Secondary outcome measures (5)

• PK of JWATM214 in the peripheral blood (qPCR) [Time frame: 1 years]
• Objective response rate (ORR). [Time frame: 1 years]
• Disease Control Rate [Time frame: 2 years]
• progression-free survival (PFS) [Time frame: 2 years]
• overall survival (OS) [Time frame: 2 years]

Eligibility criteria

Inclusion criteria

• 18-75 years-old, male or female
• Voluntarily willing to participate in the study and sign the written informed consent form
• Life expectation ≥12 weeks
• Eastern Cooperative Oncology Group (ECOG) performance status scale ≤1
• Histologically-confirmed hepatocellular carcinoma (HCC)
• No benefits from curative surgery or other local therapies are expected at screening, judged by investigators
• Radiologically-confirmed progression disease after at least one prior line of systematic treatment and limited benefits from current guideline or consensus for hepatocellular carcinoma are expected at screening, judged by investigators
• Fresh samples or FFPE, immunohistochemistry (IHC)-stained GPC-3 positive with intensity ++ or +++
• Per RECIST v1.1, at least one measurable lesion
• Manageable lung metastasis
• Barcelona Clinic Liver Cancer (BCLC) stage C or B and Child-Pugh ≤7
• No active HBV infections
• Adequate organ functions
• Adequate venous access for APH
• Non-hematological AEs induced by previous treatment must have recovered to CTCAE ≤1, except for alopecia and peripheral neuropathy
• Women of childbearing potential must agree to use an effective and reliable contraceptive method during 28 days prior to lymphodepletion to 1 year post infusion; Male patients who have not undergone vasectomy and have sexual activity with women of childbearing potential must agree to the use of a barrier contraceptive method since lymphodepletion to 1year post infusion, and sperm donation is prohibited during the study
• Women of childbearing potential must have negative serum β-hCG test result at screening and 48 hours prior to lymphodepletion

Exclusion criteria

• Cholangiocarcinoma or histological-mixed hepatocellular cholangiocarcinoma
• Active brain metastasis
• Primary lesion or infused lesions with the longest diameter ≥15cm, or other potential risk which might not be appropriate for further study treatment judged by the investigator
• Another primary malignancy within 3 years (with some exceptions for completely-resected early-stage tumors)
• Systematic autoimmune disorders requiring long-term systematic immunosuppression
• Previously treated with any genetically engineered modified T cell therapy (TCR-T/CAR-T) or other CGT
• Active HCV, HIV, or syphilis
• History of organ transplant
• Uncontrolled or active infection at screening, prior to APH, 72 hours prior to lymphodepletion or 5 days prior to JWATM214 infusion
• With severe cardiovascular disease
• History or presence of clinically-relevant CNS disorders
• Current presence of hepatic encephalopathy
• ≥G2 hemorrhage within 30 days prior to screening, or in need of long-term anticoagulants
• Active digestive ulcer or gastrointestinal bleeding within 3 months prior to screening
• Pregnant or lactating women
• Not satisfying wash-out period for APH
• Unable or unwilling to comply with the study protocol, judged by the investigator
• Other situations implying that the subject might not be appropriate to participate in the study
• Previously allergic or intolerable to JWATM214 or its components

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University — Shanghai

Identifiers

NCT: NCT05926726 · JWATM214001

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗