Phase I Study of OriC902 in Treatment of Advanced HCC

NCT06891742 | Recruiting Phase 1

• 1 other identifier: OriC902-T1
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 2

Brief Summary

This is a Phase I clinical study evaluating the safety, pharmacokinetics, and initial efficacy of a GPC3-targeted chimeric antigen receptor autologous T cell injection (OriC902) in GPC3-positive advanced hepatocellular carcinoma (HCC) subjects

Conditions

HCC

Keywords

GPC3; HCC; CART

Outcome Measures

Primary Outcomes (3)

• MTD or biologically effective dose

  SRC will select MTD or biologically effective dose

  1year

• RP2D

  SRC will select RP2D based on safety, initial efficacy (if any) and PK data

  1year

• Incidence and severity of AE and SAE,

  To evaluate the incidence and severity of AE and SAE

  2year

Secondary Outcomes (3)

• PK of OriC902

  2year

• Peripheral blood concentration of two antibodies(PD-L1&VEGF)

  2year

• Evaluate initial efficacy of OriC902

  3year

Other Outcomes (1)

• Detection biomarker

  2year

Study Arms (1)

OriC902

EXPERIMENTAL

OriC902 injection, dosage is divided into 1E6/Kg, 3E6/ Kg, 6E6/Kg, 1E7/Kg

Drug: OriC902

Interventions

OriC902 DRUG

Whole peripheral blood mononuclear cells are extracted from patients (or donors) through leukocyte separation, and then the required T cell subsets are isolated, which will become the basis for the subsequent preparation of CAR T cells

OriC902

Eligibility Criteria

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

You may qualify if:

• Understand and voluntarily sign an informed consent form (ICF) prior to conducting any assessment/procedure related to the study;
• Ages 18 to 75 at the time of signing the ICF (including 18 and 75);
• HCC was diagnosed according to the Primary Liver Cancer Diagnosis and Treatment Guidelines (2024 edition);
• Samples of liver tumor tissue or extrahepatic metastases within 1 year of signing the pre-screening informed consent were 1+ or more positive by immunohistochemical detection of GPC3 in tumor cells of at least 5% (dose escalation phase) or 10% (dose expansion phase);
• BCLC stage B HCC or BCLC stage C HCC that are not suitable for local therapy or relapse after local therapy and cannot be cured;
• Failure of standard treatment (including but not limited to targeted therapy, immunotherapy, or chemotherapy), which is determined by imaging as disease progression;
• Child-Pugh A or B7 without hepatic encephalopathy;
• An ECOG score of 0 or 1;
• The expected survival is not less than 12 weeks;
• According to RECIST 1.1, subjects have at least one measurable lesion (lesions that have received local treatment such as radiotherapy need to be identified by imaging for definite progression), and the longest diameter at baseline for CT or MRI imaging evaluation must be ≥10 mm (except lymph nodes, whose short diameter must be ≥15 mm);
• Can carry out normal venous blood collection and machine simple collection, can establish the necessary venous access for collection, no contraindications for white blood cell collection;
• The researchers judged that lymphocyte clearance therapy could be performed;
• Fertile men and women of childbearing age must consent to the use of effective contraception from the signing of the master informed consent until 2 years after the study drug use. Women of reproductive age include women before menopause and women within 2 years after menopause. Blood pregnancy tests for women of childbearing age must be negative at the time of screening.

You may not qualify if:

• Central nervous system (CNS) metastasis, meningeal metastasis, or spinal cord compression;#
• Have a history of allogeneic hematopoietic stem cell transplantation or organ transplantation;
• A history of other primary malignancies within 3 years prior to study treatment, except for the following: Adequate treatment of cured carcinoma in situ (including but not limited to cervical carcinoma in situ, breast carcinoma in situ, etc.); Adequate treatment of cured localized basal cell or squamous cell carcinoma of the skin;
• Hepatitis B surface antigen (HBsAg) positive or Hepatitis B core antibody (HBcAb) positive, and HBV-DNA \> 500 IU/mL. (For HBsAg positive or HBCAB-positive patients, antiviral therapy should be performed for at least 4 weeks before the first administration of the study drug, and antiviral therapy should be continued during the study);
• Hepatitis C virus (HCV) antibody positive and peripheral blood HCV RNA positive; Human immunodeficiency virus (HIV) antibody positive; Syphilis specific antibody positive and syphilis non-specific antibody positive; Cytomegalovirus (CMV) DNA test positive, EBV-DNA test positive;
• People who are allergic to any of the drug components to be used in this study, including but not limited to antisepsis drugs (albumin paclitaxel, cyclophosphamide, fludarabine);
• Previously received anti-tumor therapy against GPC3 targets, including but not limited to antibodies, ADCs (antibody-coupled drugs) and cell therapy;
• Investigators assessed that the intrahepatic tumor occupied more than 50% of the entire liver; The presence of main portal vein cancer thrombus or inferior vena cava cancer thrombus;
• Patients who received the following anti-tumor therapy before anapheresis: Received cytotoxic chemotherapeutic drugs within 28 days (combination chemotherapy) or 14 days (single agent chemotherapy) or 5 half-lives (whichever time the investigator determines is more appropriate); received any investigational drug/treatment within 28 days; received antibody drugs within 21 days; received a small molecule targeted drug within 14 days or 5 halflives (whichever is more appropriate in the investigator's judgment); received local treatment and/or radiotherapy within 28 days; received Chinese medicine with anti-tumor indications within 7 days;
• Major surgical treatment (other than liver space biopsy) was performed within 28 days prior to apheresis, or major surgical treatment was planned during the study period;
• Toxicity from previous antitumor therapy has not returned to grade 1 or baseline levels (according to NCI-CTCAE version 5.0), except in the following cases: alopecia, depigmentation, or partial chronic stable state grade 2 AE (such as hypothyroidism controlled by alternative therapy) and other toxicity determined by the investigator to be of no safety risk;
• Any uncontrolled active infection during the 4 weeks prior to apheresis that requires antibiotic, antiviral, or antifungal treatment;
• A history of active pulmonary tuberculosis infection within 1 year prior to anapheresis (except for subjects with a history of active pulmonary tuberculosis infection more than 1 year ago if the investigator determines that there is no evidence of active pulmonary tuberculosis at present);
• accompanied or prior history of interstitial lung disease or interstitial pneumonia; Patients with extensive lung metastasis or other severe lung disease whose lung function has been assessed by the investigator to be unable to tolerate treatment with the investigational drug;
• Have an active or past autoimmune disease that may recur (e.g., systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vasculitis and psoriasis);

Sponsors & Collaborators

• Peking University: lead
• OriCell Therapeutics Co., Ltd.: collaborator

Study Sites (2)

Beijing GoBroad Hospital

Beijing, Beijing Municipality, 100000, China

RECRUITING

Peking University Cancer Hospital & Institute

Beijing, Beijing Municipality, 100000, China

NOT YET RECRUITING

Central Study Contacts

Changsong Qi

CONTACT

13811394004; xiwangpku@126.com

Study Design

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

Model Details: The study consists of two phases: dose escalation phase and extension phase. "Accelerated titration" and "traditional 3+3 design" were used for dose escalation in the dose escalation stage. In this study, "accelerated titration" was planned for dose escalation in the low-dose phase (1.0E6/Kg and 3.0E6/ Kg). Starting from the dose group of 6.0E6/Kg, dose escalation was carried out using the "traditional 3+3 design" rule. The study was divided into screening period, treatment period and follow-up period.

Study Record Dates

• First Submitted: February 24, 2025
• First Posted: March 24, 2025
• Study Start: February 24, 2025
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): March 31, 2028
• Last Updated: March 24, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)