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

NCT05926726 | Recruiting

• 1 other identifier: JWATM214001
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (3)

• Treatment-related adverse events (AEs)

  An AE is defined as any unfavorable and unintended sign, symptom, or disease (new or worsening) temporally associated with the use of study therapy, regardless of whether or not a causal relationship with the study therapy can be determined.

  2 years

• Dose-limiting toxicities

  DLT (Dose-limiting toxicity) was an adverse event that occurred within 28 days after JWATM214 infusion that met any of the following criteria. 1. Any grade ≥3 nonhematologic toxicity associated with JWATM214 that has not resolved to ≤ grade 2 within 7 days, excluding clinically insignificant abnormalities in laboratory indicators 2. Hematologic toxicity 3. Grade ≥3 anaphylaxis 4. Grade ≥3 infection did not resolve to grade ≤2 within 7 days after anti-infective treatment. 5. ≥ grade 3 autoimmune toxicity during treatment 6. Grade ≥3 cytokine release syndrome (CRS) during treatment that did not resolve to grade ≤2 within 72 hours. 7. Grade ≥3 CAR-T cell-associated encephalopathy syndrome/immune effector cell-associated neurotoxicity syndrome (CRES/ICANS) that did not resolve to grade ≤2 within 72 hours. 8. Grade 5 events of any nonmalignant cause.

  28 days

• RP2D of JWATM214 in HCC patients

  Recommended phase 2 dose of JWATM214

  2 years

Secondary Outcomes (5)

• PK of JWATM214 in the peripheral blood (qPCR)

  1 years

• Objective response rate (ORR).

  1 years

• Disease Control Rate

  2 years

• progression-free survival (PFS)

  2 years

• overall survival (OS)

  2 years

Study Arms (1)

CAR-GPC3 T cells

EXPERIMENTAL

The safety and efficacy of JWATM214 will be evaluated in a 'BOIN'-designed dose escalation approach. 3 CAR-T dose levels will be tested in this study: 1×10\^8, 3×10\^8, and 10×10\^8, whereas the dosage 0.5×10\^8 and 30×10\^8 CAR-T cells will be selected as optional back-up doses for potential escalation or de-escalation.

Biological: CAR-GPC3 T cells

Interventions

CAR-GPC3 T cells BIOLOGICAL

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.

CAR-GPC3 T cells

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• RenJi Hospital: lead

Study Sites (1)

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

Shanghai, 200127, China

RECRUITING

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Study Officials

• Qiang Xia, Prof. MD

  Dept. Liver Surgery, Renji Hospital, School of Medicine, SJTU

  STUDY CHAIR

• Hao Feng, MD.,Ph.D.

  Dept. Liver Surgery, Renji Hospital, School of Medicine, SJTU

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Hao Feng, MD.,Ph.D

CONTACT

008615000901110; surgeonfeng@live.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 4, 2023
• First Posted: July 3, 2023
• Study Start: January 1, 2023
• Primary Completion: December 31, 2025
• Study Completion (Estimated): December 31, 2026
• Last Updated: July 3, 2023

Record last verified: 2023-05

Locations

CN (1)