Study Of B7H3 CAR-T Cells in Treating Advanced Liver Cancer

NCT05323201 | Recruiting Phase 1

• 1 other identifier: XYFY2021-KL272-02
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

This is single center, open-label phase I/II, non-randomized study which will enroll patients with recurrent advanced hepatocellular carcinoma to evaluate the safety, feasibility, and efficacy of fully human B7H3 CAR-T in treating hepatocellular carcinoma.

Conditions

Hepatocellular Carcinoma

Keywords

Fully human B7H3 CAR-T; Recurrent Advanced Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (2)

• Safety of fhB7H3.CAR-T cells

  Adverse events, including the type, frequency, severity and duration, such as cytokine release syndrome (CRS), on-target off-tumor, immune effector cell-associated neurotoxicity syndrome, will be monitored and assessed.

  1 month

• Objective response of fhB7H3.CAR-T cells

  Objective response rate (ORR) including complete response (CR), partial response (PR), and/or stable disease, will be determined by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria. Complete Response (CR): disappearance of all target lesions, all target nodules must be reduced to normal size (short axis \<10 mm). Partial Response (PR): \>=30% decrease in the sum of the longest diameter of target lesions. Stable Disease (SD): no response or less response than Partial or Progressive. Progressive Disease (PD): 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

  1 month

Secondary Outcomes (1)

• In vivo persistence of fhB7H3.CAR-T cells

  1 month

Other Outcomes (2)

• Progress free survival (PFS)

  up to 5 years

• Overall survival (OS)

  up to 5 years

Study Arms (1)

fhB7H3.CAR-T cells

EXPERIMENTAL

In phase I study , 9 enrolled patients diagnosed with advanced liver cancer will receive one-time transhepatic arterial infusion of fhB7H3.CAR-Ts at the doses of 1×10\^6/kg, 3×10\^6/kg and 5×10\^6/kg, 3 patients for each dose. To further confirm the therapeutic efficacy, in phase II study, 6 enrolled patients will receive an optimal dose (balancing effectiveness and toxicity) of fhB7H3.CAR-Ts.

Biological: fhB7H3.CAR-Ts; Drug: Fludarabine; Drug: Cyclophosphamide

Interventions

fhB7H3.CAR-Ts BIOLOGICAL

fhB7H3.CAR-Ts will be transhepatic arterial infused after lymphodepletion. Three dose levels will be evaluated: Dose Level 1 (1×10\^6/kg), dose Level 2 (3×10\^6/kg) and dose Level 3 (5×10\^6/kg). If dose limiting toxicities (DLTs) are observed in each doses, Dose Level -1 (0.5×10\^6/kg /infusion) will be evaluated.

Also known as: B7H3 targeting chimeric antigen receptor T cells

fhB7H3.CAR-T cells

Fludarabine DRUG

30 mg/m2 i.v. for 3 consecutive days (Day -5\~Day -3)

Also known as: FLUDARA

fhB7H3.CAR-T cells

Cyclophosphamide DRUG

750 mg/m2 i.v. for once (Day -5)

Also known as: Cytoxan

fhB7H3.CAR-T cells

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects should be 18-70 years old.
• Subject has adequate performance status as defined by ECOG score of≤ 2.
• Expected life expectancy is no less than 12 weeks.
• Subjects must have histologically or cytologically confirmed unresectable, recurrent and / or metastatic hepatocellular carcinoma (HCC). And tumor tissues are measured positive for B7H3 expression.
• Child-Pugh A, B grade.
• Blood routine:
• white blood cell count≥ 2.5 × 10\^9 / L; hemoglobin≥ 9 g/dL; platelet count≥ 50 × 10\^9 / L; lymphocyte proportion≥ 15 %;
• Adequate organ function. Patients' main organs ( heart, lung, liver, kidney, etc. ) function well:
• ALT and AST≤ 5 × ULN; ALB≥ 30 g/L； Total bilirubin≤ 2.5 × ULN； Serum creatinine\< 220μmol/L; Indoor oxygen saturation ≥ 95 %; Left ventricular ejection fraction≥ 40%;
• No allergic reaction to contrast agents.
• Procurement and T-cell production eligibility: a previously evaluation confirmed autologous peripheral blood mononuclear cells can be used for T-cell production.
• Patients or their legal guardians voluntarily participate in and sign the informed consent form.

You may not qualify if:

• The subject is a pregnant or lactating woman.
• The subjects have infectious diseases (such as HIV, syphilis, active tuberculosis, etc.);
• The subject has active infection or coagulation dysfunction.
• Subjects with previous hepatic encephalopathy.
• The subject is on anticoagulation or antiplatelet therapy.
• The subject is an organ transplant or waiting for transplant.
• Subjects with mental or psychological diseases who cannot cooperate with treatment and efficacy evaluation.
• The subjects are highly allergic or have a history of severe allergies.
• The subject has received chemotherapy/radiotherapy within the past 4 weeks.
• The subject has a history of cellular immunotherapy or antibody therapy.
• The subject is receiving systemic hormone therapy.
• Subjects with systemic infection or severe local infection requiring anti-infection treatment.
• The subject has dysfunction of important organs such as heart, lung, brain, liver, and kidney.
• The subject is participating in other clinical research.
• The doctor believes that there are other reasons not to be included in the treatment.

Sponsors & Collaborators

• The Affiliated Hospital of Xuzhou Medical University: lead
• Xuzhou Medical University: collaborator
• IIT MediTech Co. Ltd: collaborator

Study Sites (1)

The Affiliated Hospital of Xuzhou Medical University

Xuzhou, Jiangsu, 221002, China

RECRUITING

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

fludarabine; fludarabine phosphate; Cyclophosphamide

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

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Design

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

Study Record Dates

• First Submitted: February 13, 2022
• First Posted: April 12, 2022
• Study Start: February 10, 2022
• Primary Completion: February 10, 2024
• Study Completion (Estimated): February 10, 2027
• Last Updated: April 12, 2022

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)