A Study to Evaluate Safety and Efficacy of Armored CAR-T Cell Injection C-CAR031 in Advanced Hepatocellular Carcinoma

NCT05155189 | Recruiting Phase 1

• 1 other identifier: 0921-028
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 2

Brief Summary

A study that aimed to assess the safety and anti-tumor activity of CCAR031 injection in unresectable HCC patients.

Conditions

Hepatocellular Carcinoma

Keywords

Liver Cancer

Outcome Measures

Primary Outcomes (2)

• TEAEs

  treatment emergent adverse events

  start pretreatment to 12 months

• AESIs

  adverse events of special interest

  start pretreatment to 12 months

Secondary Outcomes (11)

• objective response rate by RECIST 1.1

  at Weeks 6, 12, and 18 and Months 6, 9, and 12 after cell infusion

• disease control rate by RECIST 1.1

  at Weeks 6, 12, and 18 and Months 6, 9, and 12 after cell infusion

• duration of response by RECIST 1.1

  at Weeks 6, 12, and 18 and Months 6, 9, and 12 after cell infusion

• progression-free survival by RECIST 1.1

  The efficacy is evaluated at Weeks 6, 12, and 18 and Months 6, 9, and 12 after cell infusion.-

• objective response rate by mRECIST

  The efficacy is evaluated at Weeks 6, 12, and 18 and Months 6, 9, and 12 after cell infusion.-

Study Arms (4)

C-CAR031

EXPERIMENTAL

Autologous C-CAR031 administered by intravenous (IV) infusion

Biological: C-CAR031

C-CAR031 combined with Lenvatinb

EXPERIMENTAL

Autologous C-CAR031 combination with Lenvatinib

Biological: C-CAR031; Drug: Lenvatinib

C-CAR031 combined with Regorafenib

EXPERIMENTAL

Autologous C-CAR031 combination with Regorafenib

Biological: C-CAR031; Drug: Regorafenib (BAY 73-4506)

C-CAR031 combined with Durvalumab

EXPERIMENTAL

Autologous C-CAR031 combination with Durvalumab

Biological: C-CAR031; Drug: Durvalumab

Interventions

C-CAR031 BIOLOGICAL

Targeting GPC3 armored CART cell injection (C-CAR031)

C-CAR031; C-CAR031 combined with Durvalumab; C-CAR031 combined with Lenvatinb; C-CAR031 combined with Regorafenib

Lenvatinib DRUG

Tyrosine kinase inhibitors

C-CAR031 combined with Lenvatinb

Regorafenib (BAY 73-4506) DRUG

Tyrosine kinase inhibitors

C-CAR031 combined with Regorafenib

Durvalumab DRUG

Immune checkpoint inhibitors, ICIs

C-CAR031 combined with Durvalumab

Eligibility Criteria

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

You may qualify if:

• Voluntary participation and able to sign the informed consent form
• \. Aged 18 to 75 years at screening
• \. Patients with histologically confirmed hepatocellular carcinoma (HCC) who meet the following requirements: a. Barcelona Clinic Liver Cancer Stage B or C (BCLC B/C) b. Child-Pugh score ≤ 6 c. GPC3 is possibly expressed in tumor tissues
• \. Patients with relapsed / progressive disease after at least one prior standard systemic therapy for HCC, or ineligible to accept/unable to tolerate the systemic therapies. Standard systemic therapies may include targeted drugs (such as Sorafenib, Lenvatinib, Donafenib, Apatinib), immune checkpoint inhibitors (such as Atezolizumab, Pembrolizumab, Camrelizumab, Sintilimab, Nivolumab, Toripalimab, Tislelizumab) or chemotherapeutic drugs (such as Oxaliplatin and 5-Fu). Subjects in theC-CAR031 plus Lenvatinib group must meet the following criteria: (1)have not received prior Lenvatinib therapy; (2) Progression or intolerance to one prior line of systemic therapy containing both immune checkpoint inhibitors and VEGF/VEGFR- targeted agents. Subjects in the C-CAR031 combination with Regorafenib group must meet the following criteria: (1)have not received prior Regorafenib therapy; (2) Progression or intolerance to one prior line of systemic therapy containing both immune checkpoint inhibitors and VEGF/VEGFR- targeted agents. Subjects in theC-CAR031 plus Durvalumab group must meet the following criteria:(1) Progression or intolerance to one prior line of systemic therapy containing both immune checkpoint inhibitors and VEGF/VEGFR-targeted agents; (2) no prior immune-related toxicity leading to permanent discontinuation of immunotherapy;(3) no history of ≥ Grade 3 immune-related adverse events (irAEs), or any grade immune-related neurological/ocular AEs. (Note: Subjects with ≤ Grade 2 endocrine AEs may enroll if asymptomatic on stable replacement therapy, excluding those: a. requiring non-corticosteroid immunosuppressants, b. experiencing AE recurrence upon immunotherapy rechallenge, c. or using corticosteroids at \>10 mg/day prednisone or equivalent.) (4) All AEs associated with prior immunotherapy must have resolved or returned to pre-treatment levels prior to screening; (5) Body weight more than 30 kg.
• \. At least one measurable target lesion (as per RECIST v1.1)
• \. WHO/ECOG performance status (PS) score of 0 or 1 point
• \. Expected survival ≥ 12 weeks
• \. Left ventricular ejection fraction (LVEF) by echocardiography ≥ 45%
• \. No active pulmonary infection; no known history of pneumonitis requiring steroids; absence of acute onset or progressive pneumonitis at baseline.
• \. Laboratory tests: a. Absolute neutrophil count (ANC) ≥ 1.0 × 109/L b. Lymphocyte count ≥ 0.4 × 109/L c. Platelet count ≥ 60 × 109/L d. Hemoglobin ≥ 80 g/L e. Total bilirubin (TBIL) ≤ 2 × upper limit of normal (ULN) f. AST and ALT ≤ 5 × ULN g. Serum creatinine ≤ 1.5 × ULN h. Prothrombin time (PT): prolonged PT ≤ 4 s
• \. Patients without history of HBV infection, or with HBV DNA \< 2000 IU/mL (or 10000 copies/mL) at screening who agree to receive anti-virus therapies throughout the study according to the guidelines
• \. Negative serum or urine pregnancy test results for females of child-bearing age at screening; In addition, they should agree to take effective contraceptive measures throughout the study
• \. Patients who agree to abstain from drinking throughout the study

You may not qualify if:

• \. History of severe allergic or hypersensitivity to DMSO. Subjects with known allergies to the active components of Lenvatinib, Regorafenib, or Durvalumab will be excluded from respective combination treatment groups.
• \. History of liver transplantation
• \. History of prior cell therapy
• \. Tumor volume \> 50% of the liver.
• \. portal stem vein tumor thrombus
• \. Moderate to severe ascites.
• \. Metastases to bones or central nervous system (CNS), or involved CNS diseasesincluding hepatic encephalopathy, epilepsy, cerebrovascular accidents, etc.
• \. Receipt of radiotherapy within 6 weeks prior to apheresis
• \. Receipt of Local therapy (such as surgery, ablation, and intervention) within 4 weeks prior to apheresis or presence of unhealed wounds before apheresis
• \. Other history of primary cancers, excluding:a. Nonmelanoma skin cancer cured by resection (such as basal cell carcinoma) b. Cured carcinoma in situ (such as cervical cancer, bladder cancer, and breast cancer)
• \. Active hepatitis C virus infection (HCV RNA positive)
• \. Syphilis infection
• \. History of active/immunodeficient diseases (including but not limited to HIV, systemic lupus erythematosus, inflammatory bowel disease, rheumatoid arthritis, myasthenia gravis, Graves' disease, and hypophysitis; excluding: vitiligo or alopecia, hypothyroidism in patients with stable medical conditions after hormone replacement therapy, any chronic skin conditions that need no systemic treatment, and other diseases judged by the investigator to be of no clinical significance)
• \. Persistent and active infections (excluding prophylactic anti-infectives)
• \. Uncontrolled hypertension, diabetes, arrhythmia, and symptomatic congestive heart failure

Sponsors & Collaborators

• Zhejiang University: lead

Study Sites (2)

the First Affiliated Hospital, School of Medicine, Zhejiang University

Hangzhou, Zhejiang, 310003, China

RECRUITING

The first affiliated hospital of Zhengzhou University

Zhengzhou, China

RECRUITING

MeSH Terms

Conditions

Carcinoma, Hepatocellular; Liver Neoplasms

Interventions

lenvatinib; regorafenib; durvalumab

Condition Hierarchy (Ancestors)

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

Central Study Contacts

Qihan Fu

CONTACT

18268173309; ayfuqihan@126.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: professor

Model Details: Four Groups Assignment

Study Record Dates

• First Submitted: December 7, 2021
• First Posted: December 13, 2021
• Study Start: February 21, 2022
• Primary Completion: May 1, 2026
• Study Completion (Estimated): May 1, 2041
• Last Updated: January 21, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)