A Study to Evaluate C-CAR031 in Glypican-3 (GPC3)+ Advanced/Recurrent Hepatocellular Carcinoma (HCC)

NCT06590246 | Recruiting Phase 1

• 1 other identifier: 0921-041
• Study Type: interventional
• Target: 121
• Locations: 1 country
• Sites: 2

Brief Summary

This single-arm, open-label multicenter Phase I/II study will evaluate the safety, tolerability, anti-tumor activity, pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of C-CAR031 in adult participants with GPC3+ advanced/recurrent HCC, who have progressed or are intolerant to at least two prior lines of standardized systemic therapy, and lack of other effective treatments.

Conditions

Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (10)

• Phase I: Safety and tolerability

  • Incidence, correlation and severity of adverse events (AEs).

  Throughout the study period, which extends up to 24 months after the administration of C-CAR031.

• Phase I: Safety and tolerability

  • Incidence, correlation and severity of serious adverse events (SAEs)

  Throughout the study period, which extends up to 24 months after the administration of C-CAR031.

• Phase I: Safety and tolerability

  • Incidence, correlation and severity of adverse events of special interest (AESIs)

  Throughout the study period, which extends up to 24 months after the administration of C-CAR031.

• Phase I: Safety and tolerability

  • Incidence and severity of dose limiting toxicities (DLTs)

  Throughout the 28 days post C-CAR031 infusion.

• Phase I: Safety and tolerability

  • Changes from baseline in vital signs (including temperature, systolic and diastolic blood pressure, pulse, respiratory rate, blood oxygen saturation) that are abnormal and of clinically significance.

  Throughout the study period, which extends up to 24 months after the administration of C-CAR031.

• Phase I: Safety and tolerability

  • Changes from baseline in physical examination (including the general appearance, respiratory, cardiovascular, abdomen, skin, head and neck, lymph nodes, thyroid, musculoskeletal, and neurological systems) that are abnormal and of clinically significance.

  Throughout the study period, which extends up to 24 months after the administration of C-CAR031.

• Phase I: Safety and tolerability

  • Changes from baseline in Eastern Cooperative Oncology Group (ECOG) score that are abnormal and of clinically significance (ECOG performance status score above 1).

  Throughout the study period, which extends up to 24 months after the administration of C-CAR031.

• Phase I: Safety and tolerability

  • Changes from baseline in 12-lead electrocardiograms (ECGs) that are abnormal and of clinically significance.

  Throughout the study period, which extends up to 24 months after the administration of C-CAR031.

• Phase I: Safety and tolerability

  • Changes from baseline in laboratory test results (including the clinical chemistry, haematology, coagulation, urinalysis, serology, pregnancy assessments) that are abnormal and of clinically significance.

  Throughout the study period, which extends up to 24 months after the administration of C-CAR031.

• Phase II: Anti-tumor activity

  • Objective response rate (ORR) assessed by independent review committee (IRC) and evaluated according to Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 criteria

  Throughout the study period, which extends up to 24 months after the administration of C-CAR031.

Secondary Outcomes (44)

• Phase I: Pharmacokinetics

  Throughout the study period, which extends up to 24 months after the administration of C-CAR031.

• Phase I: Pharmacokinetics

  Throughout the study period, which extends up to 24 months after the administration of C-CAR031.

• Phase I: Pharmacokinetics

  Throughout the study period, which extends up to 24 months after the administration of C-CAR031.

• Phase I: Pharmacokinetics

  Throughout the 28 days post C-CAR031 infusion.

• Phase I: Pharmacokinetics

  Throughout the study period, which extends up to 24 months after the administration of C-CAR031.

Study Arms (1)

C-CAR031

EXPERIMENTAL

* Dose escalation section (Part A1) utilizes a '3+3' design to explore the recommended dose for expansion (RDE). Initially, two dose levels (DLs) will be assessed. Patients in the dose escalation section will receive autologous C-CAR031 via intravenous (IV) infusion at DL1 and DL2. * Dose expansion (Part A2) will evaluate the safety and tolerability of C-CAR031 to determine RP2D to be used in Part B (Phase II). Patients in the dose expansion section will receive autologous C-CAR031 via IV infusion at the RDE. * The patients in the Phase II section (Part B) will receive autologous C-CAR031 via IV infusion at the RP2D, which will be determined after Part A by SRC.

Biological: Armored and GPC3-targeted autologous CAR T-cell

Interventions

Armored and GPC3-targeted autologous CAR T-cell BIOLOGICAL

Armored and GPC3-targeted autologous CAR T-cells, single infusion intravenously.

Also known as: C-CAR031

C-CAR031

Eligibility Criteria

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

You may qualify if:

• The participant voluntarily participates in the study, and the individual or their legal guardian signs the informed consent form (ICF).
• \~ 75 years of age at the time of signing ICF.
• Clinical trial participants with advanced HCC confirmed by histopathological or cytological examination with the following requirements (no mixed HCC-cholangiocarcinoma permitted):
• Barcelona Clinic Liver Cancer (BCLC) stage C or B (not amenable to surgery/local treatment, includes ablative therapy, interventional and radiation therapy) or stage II-III ( not amenable to surgery/local treatment, includes ablative therapy, interventional and radiation therapy) per China liver cancer staging (CNLC).
• Child-Pugh score ≤ 6.
• Participants must have a GPC3-positive tumor as determined by a central laboratory using an analytically validated IHC assay. Participants with unknown GPC3 status are not eligible for this study.
• Participants who have progressed or are intolerant to at least two prior lines of standardized systemic therapy, and lack of other effective treatments; Systemic therapy intolerance is defined as: drug-related adverse reactions or side effects caused by systemic therapy (including but not limited to targeted therapy, immunotherapy) in patients with HCC that prevent patients from continuing treatment.
• At least one measurable target lesion (as defined by RECIST v1.1) that has not undergone prior local therapies such as radiotherapy (excluding lesions with radiologically confirmed progression after local therapy), and has not been utilized for research pre-screening biopsies (if only one target lesion exists and must undergo tissue biopsy, baseline tumor imaging must be performed at least 14 days after the biopsy).
• ECOG performance status score of 0 or 1.
• Minimal life expectancy ≥12 weeks, per the Investigator's discretion.
• The left ventricular ejection fraction (LVEF) measured by echocardiography ≥45% and reported as non-impaired. Measure must be within 28 days prior to apheresis.
• The laboratory testing results meet the following study requirements. Blood routine examination
• \*Absolute Neutrophil Count (ANC) ≥1.0×10\^9/L.
• Absolute Lymphocyte count ≥ 0.3×10\^9/L.
• \*Platelet count ≥ 75×10\^9/L.

You may not qualify if:

• Known life-threatening allergies, hypersensitivity, or intolerance to the CAR-T product or its excipients, including dimethyl sulfoxide (DMSO).
• Known allergies to lymphodepleting agents, including fludarabine and/or cyclophosphamide.
• History of hepatic encephalopathy within past 6 months prior to apheresis or requirement for medications to prevent or control encephalopathy (eg, lactulose, rifaximin, etc infused for purposes of hepatic encephalopathy).
• Participants with central nerve system (CNS) diseases such as epilepsy, severe cerebral vascular stenosis, or those who have had a cerebral infarction or other cerebral vascular accidents within 6 months, or other diseases with obvious neurological symptoms (including mental illnesses).
• Uncontrolled or intercurrent cardiac or pulmonary diseases, including but not limited to, chronic obstructive pulmonary disease with obvious symptoms, and moderate or above persistent asthma, with a known history of non-infectious pneumonia requiring steroid treatment, or those presenting with acute exacerbation or progressive non-infectious pneumonia at baseline, unstable angina, severe arrhythmia, severe non-ischemic cardiomyopathy history or myocardial infarction or cardiac vascular surgery treatment occurred within 6 months.
• History of organ transplant including liver.
• Prior treatment with:
• Any CAR-T therapy. OR
• Any therapy that is targeting GPC3.
• The tumor volume is larger than 50% of the liver tissue.
• Main portal vein cancer embolus (Vp4, cancer embolus in the main trunk of the portal vein, with or without blood flow) on pre-LDC imaging.
• History of deep vein thrombosis, pulmonary embolism, or any other significant thromboembolism (venous port or catheter thrombosis or superficial venous thrombosis are not considered "significant") during the 3 months prior to apheresis.
• Clinically meaningful ascites, defined as any ascites requiring non-pharmacologic intervention (eg, paracentesis) to maintain symptomatic control, within 6 months prior to apheresis. Participants on stable doses of diuretics for ascites for ≥ 2 months prior to apheresis are eligible.
• Uncontrolled pleural effusion or pericardial effusion requiring recurrent drainage procedures (once monthly or more frequently).
• Cancer-related spinal cord compression, leptomeningeal disease, or brain metastases unless asymptomatic, treated, and stable radiologically (defined as 2 brain images, \[both after treatment\], should both be obtained at least 4 weeks apart and show no evidence of intracranial progression) and resolved or stable clinically; not requiring continuous corticosteroids at a dose above10 mg/day prednisone or equivalent for at least 4 weeks prior to apheresis.

Sponsors & Collaborators

• Shanghai AbelZeta Ltd.: lead

Study Sites (2)

ZhongShan Hospital Fudan University

Shanghai, Shanghai Municipality, 200032, China

RECRUITING

The First Affiliated Hospital, Zhejiang University School of Medicine

Hanzhou, Zhejiang, 310003, 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

Central Study Contacts

Andy Zou

CONTACT

+86-21-54069990; Andy.Zou@abelzeta.com

Nicole Shen

CONTACT

+86-21-54069993; yinghua.shen@abelzeta.com

Study Design

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

Study Record Dates

• First Submitted: September 1, 2024
• First Posted: September 19, 2024
• Study Start: September 30, 2024
• Primary Completion (Estimated): April 30, 2030
• Study Completion (Estimated): April 30, 2043
• Last Updated: January 2, 2026

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)