A Phase 1, Single-arm, Open-label, Dose-escalation Study of JWATM204 as T Cell-targeted Immunotherapy in the Treatment Amongst Subjects With Advanced Hepatocellular Carcinoma

NCT06144385 | Unknown Phase 1

• 1 other identifier: JWATM204001
• Study Type: interventional
• Target: 20
• 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 GPC3-directed CAR-T in patients with advanced hepatocellular carcinoma refractory to prior systematic treatments.

Conditions

Liver Carcinoma; Hepatic Cell Carcinoma

Outcome Measures

Primary Outcomes (3)

• Rate of dose-limiting toxicities (DLTs)

  Dose-limiting toxicity (DLT) is defined as an adverse event that occurred within 28 days after JWATM204 infusion that met any of the following criteria. Any grade ≥3 nonhematologic toxicity associated with JWATM204 that has not resolved to ≤ grade 2 within 7 days, excluding clinically insignificant abnormalities in laboratory indicators Hematologic toxicity Grade ≥3 anaphylaxis Grade ≥3 infection did not resolve to grade ≤2 within 7 days after anti-infective treatment. ≥ grade 3 autoimmune toxicity during treatment Grade ≥3 cytokine release syndrome (CRS) during treatment that did not resolve to grade ≤2 within 72 hours. 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. Grade 5 events of any nonmalignant cause.

  28 days

• Rate and severity of adverse events (AEs) and severe adverse events (SAEs)

  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

• Rate and severity of clinically-significant abnormalities in laboratory testings

  Clinically-significant abnormalities in laboratory testings.

  2 years

Secondary Outcomes (5)

• Copy number of the vector transgene of JWATM204 in peripheral blood

  1 year

• Objective response rate (ORR)

  2 years

• Disease Control Rate (DCR)

  2 years

• Progression-free survival (PFS)

  2 years

• Overal survival (OS)

  2 years

Study Arms (1)

CAR-GPC3 T cells

EXPERIMENTAL

The safety and efficacy of JWATM204 will be evaluated in a Bayesian Optimal Interval Design (BOIN) dose escalation approach. 3 CAR-T dose levels will be tested in this study: 1×10\^8, 3×10\^8, 10×10\^8, and 30×10\^8 CAR-T cells will be explored.

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 JWATM204 . During JWATM204 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 JWATM204 by intravenous (IV) injection.

Also known as: JWCAR204

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 available options for hepatocellular carcinoma are expected at screening, judged by investigators
• Fresh samples or formalin-fixed paraffin-embedded (FFPE) samples, immunohistochemistry (IHC)-stained GPC-3 positive
• Per RECIST v1.1, at least one measurable lesion
• Barcelona Clinic Liver Cancer (BCLC) stage C or B and Child-Pugh ≤7
• No active infections of hepatitis B virus
• Adequate organ functions
• Adequate venous access for apheresis
• 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

You may not qualify if:

• Active brain metastasis
• Primary lesion or infused lesions with the longest diameter ≥15 cm, 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 nor other cell-gene therapy
• Active infections of hepatitis C virus (HCV), human immunodeficiency virus (HIV), or syphilis
• Uncontrolled or active infection at screening, prior to apheresis, 72 hours prior to lymphodepletion or 5 days prior to JWATM204 infusion
• With severe cardiovascular disease History or presence of clinically-relevant central nervous system (CNS) disorders
• With clinically-significant CNS disorders
• Current presence of or previously with hepatic encephalopathy
• ≥G2 hemorrhage within 30 days prior to screening, or in need of long-term anticoagulants
• Pregnant or lactating women
• Not satisfying pre-defined wash-out period for apheresis
• Received plasma exchange within 14 days prior to apheresis
• Unable or unwilling to comply with the study protocol, judged by the investigator, or other situations implying that the subject might not be appropriate to participate in the study

Sponsors & Collaborators

• Shanghai Ming Ju Biotechnology Co., Ltd.: lead

Study Sites (1)

Tao Zhang

Wuhan, Hubei, 430022, 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

• Tao Zhang, MD, PhD

  Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Tao Zhang, MD, PhD

CONTACT

+86 027-85726375; 1277577866@qq.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 15, 2023
• First Posted: November 22, 2023
• Study Start: March 24, 2022
• Primary Completion: March 1, 2024
• Study Completion: December 1, 2024
• Last Updated: January 2, 2024

Record last verified: 2023-12

Locations

CN (1)