Clinical Study of QH104 Cell Injection for the Treatment of Meningeal Metastases of B7H3+ Solid Tumors

This is an open, single-arm, single-center, interventional clinical study. It is planned to enroll 3-6 patients with meningeal metastases from B7H3+ solid tumors and to explore, on a small scale, the efficacy of local injection of allogeneic B7H3 CAR-γδ T cells (3*107/dose) for the treatment of patients with meningeal metastases from B7H3+ solid tumors.

Study Overview

• Status: Completed
• Conditions: Solid Tumor; Meningeal Metastasis
• Intervention / Treatment: Biological: QH104 Cell injection

Detailed Description

This study is an open, single-arm, single-center, interventional clinical study. It is planned to enroll 3-6 patients with meningeal metastases from B7H3+ solid tumors and to explore, on a small scale, the clinical response to local injection of allogeneic B7H3 CAR-γδ T cells (3*107/dose) for the treatment of patients with meningeal metastases from B7H3+ solid tumors. During the period of cell therapy, the enrolled subjects may be given additional multiple infusions of cells, after imaging, neurological function, cerebrospinal fluid cytology or the investigator's assessment of the potential benefit of continuing cell therapy. It is recommended that the frequency of multiple infusions be 2 weeks each, and the interval between infusions can be adjusted at a later stage based on the PK and clinical symptoms of the subject after infusion.

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100021
      • Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥18 years;
2. Have a histologically or cytologically confirmed solid malignant tumor with positive B7H3 expression;
3. ECOG ≤ 2 or KPS ≥ 60;
4. Life expectancy ≥ 8 weeks as assessed by the investigator;
5. Meningeal metastases (or with brain parenchymal metastases) from any solid malignancy that is refractory to standard treatment or for which no standard treatment is available and positive cerebrospinal fluid (CSF) cytology;

6. Substantially normal bone marrow reserve function and normal hepatic and renal function (laboratory tests are required to be satisfied prior to first treatment with QH104 Cell Injection):

   White blood cell count (WBC) ≥ 3 x 109/L; Lymphocyte count (LY) ≥ 0.8 x 109/L; Hemoglobin (Hb) ≥ 90 g/L; Platelet (PLT) ≥90×109/L; Albumin transaminase (ALT) & albumin transaminase (AST) < 1.5 x ULN; Serum creatinine (Cr) < 1.5 x ULN; Total bilirubin < 1.5 x ULN; PT & PTT ≤ 1.25 × ULN.

7. Pregnancy test should be negative for women of childbearing potential and both men and women agree to use effective contraception during treatment and for 1 year thereafter;
8. Be able to understand the requirements and matters of the trial and be willing to participate in the clinical study as required;
9. Sign the trial informed consent form.

Exclusion Criteria:

1. Targeted CNS irradiation within 7 days prior to receiving the first QH104 infusion;
2. Uncontrolled comorbidities including, but not limited to: persistent or active infections, symptomatic congestive heart failure, unstable angina, cardiac arrhythmias, or psychiatric/social conditions that would limit the patient's ability to comply with study requirements;
3. Has a known psychiatric or substance abuse disorder that would interfere with cooperation with trial requirements;
4. Is receiving treatment with any other investigational drug;
5. Have a confirmed diagnosis of an immunodeficiency disorder;
6. Have an active infection requiring systemic treatment;
7. Inability to perform an MRI;
8. Serious cardiovascular compromise: history of New York Heart Association (NYHA) class II or greater congestive heart failure, unstable angina, myocardial infarction or stroke within 6 months of first dose, or arrhythmia requiring treatment at screening;
9. Allergy to immunotherapy and related cells;
10. Prior treatment with CAR-T and other immune cell therapy;
11. Other reasons, in the opinion of the investigator, why participation in this study is not appropriate.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: QH104 cell Injection(Allogenic B7H3 CAR-γδT cell); Plan to enroll 3 to 6 patients with meningeal metastasis of B7H3+ solid tumor with single or multiple local injections of allogenic B7H3 CAR-γδ T cells (3*107/ dose)	Biological: QH104 Cell injection; Patients will first be pre-screened for B7H3 expression of tumor and exist Meningeal Metastases.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical response	Evaluate the clinical response of QH104 cell injection in treating B7H3+ solid tumor meningeal metastases according to the Response Assessment in Neuro-Oncology (RANO) criteria	day14

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival(OS)	OS is defined as the time from QH104 cells infusion to the date of death.	3month,6month,12month
Incidence of Adverse Events (AEs)	AE is defined as any adverse medical event from the date of infusion to 14 days after QH104 infusion. Among them, cytokine release syndrome (CRS) and immune cell-associated neurotoxicity syndrome (ICANS) were graded according to American Society for Transplantation and Cellular Therapy (ASTCT) criteria, graft-versus host disease (GVHD) according to criteria defined by the Mount Sinai Acute GVHD International Consortium. Other AEs were graded according to common terminology criteria for adverse events (CTCAE) v5.0.	day14 and day 28
quality of life(QoL) score	Use the M.D. Anderson Symptom Inventory for Brain Tumors (MDASI-BT) to evaluate quality of life for all enrolled subjects, with assessments conducted prior to each cell infusion and during follow-up.	day 14 and day 28
Pharmacokinetic (PK)	Assess the pharmacokinetics (PK) of QH104 cell infusion in B7H3+ solid tumor meningeal metastases by monitoring the quantity of CAR+ cells, their subpopulations following QH104 cell reinfusion.	At days 0, 1, 3, 7, and 14
Pharmacodynamic (PD)	Assess the pharmacodynamics (PD) of QH104 cell infusion in B7H3+ solid tumor meningeal metastases by monitoring the quantity of CAR+ cells, their subpopulations, differentiation, exhaustion, and cytokine changes in the cerebrospinal fluid following QH104 cell reinfusion.	At days 0, 1, 3, 7, and 14

Collaborators and Investigators

• Sponsor: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
• Investigators: Principal Investigator: Ning Li, Ph.D, Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2024
• Primary Completion (Actual): May 31, 2025
• Study Completion (Actual): January 28, 2026

Study Registration Dates

• First Submitted: March 17, 2024
• First Submitted That Met QC Criteria: September 9, 2024
• First Posted (Actual): September 19, 2024

Study Record Updates

• Last Update Posted (Actual): January 29, 2026
• Last Update Submitted That Met QC Criteria: January 28, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: B7H3 positive；; CAR-γδT cell
• Additional Relevant MeSH Terms: Nervous System Diseases; Neoplasms by Site; Neoplasms; Nervous System Neoplasms; Meningeal Neoplasms; Central Nervous System Neoplasms; Meningeal Carcinomatosis
• Other Study ID Numbers: QH10402-LMD-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No