QH101 Cell Injection in Patients With Brain, Brain (Spinal) Meninges, and Spinal Cord Metastatic Malignant Solid Tumors

Exploratory Clinical Study of Dose Escalation for QH101 Cell Injection in Patients With Brain, Brain (Spinal) Meninges, and Spinal Cord Metastatic Malignant Solid Tumors Three Dose Groups Are Established: 1×10⁷ enTCR Vδ2T Cells Per Infusion (Low Dose), 3×10⁷ enTCR Vδ2T Cells Per Infusion (Medium Dose), and 6×10⁷ enTCR Vδ2T Cells Per Infusion (High Dose). The Dose Escalation Rules Are as Follows: The First Enrolled Subject Receives Low-dose Cell Infusion. If no Dose-limiting Toxicity (DLT) Events Occur After Infusion, the Second Enrolled Subject Receives Medium-dose Infusion; the Medium and Hig

QH101 is an allogeneic TCR-enhanced Vδ2 T cell therapy product engineered to express BTN protein-specific binding elements on the cell surface. This innovative approach harnesses the natural cytotoxic capabilities of Vδ2 T cells while augmenting their ability to recognize BTN proteins, thereby significantly improving tumor cell elimination efficiency. Notably, QH101 is designed without co-stimulatory signal domains or the CD3ζ domain, which prevents T cell exhaustion from overactivation and effectively enhances in vivo persistence.

This is an early-phase clinical study conducted to initially evaluate the safety, tolerability, and preliminary biological activity of QH101, an allogeneic TCR-enhanced Vδ2 T cell therapy, in patients with advanced solid tumors who have exhausted standard treatment options. The study adopts an open-label, non-randomized design to fully observe the in vivo performance of QH101, which is engineered to express BTN protein-specific binding elements without co-stimulatory signal domains or the CD3ζ domain.

Prior to QH101 infusion, eligible patients will receive a standardized lymphodepletion regimen to create a favorable immune microenvironment for the homing, expansion, and persistence of infused Vδ2 T cells. QH101 will be administered via intravenous infusion, with a gradual dose-escalation strategy implemented to explore the safe dose range. Throughout the study, patients will undergo close clinical monitoring to track any adverse events associated with the therapy, with a particular focus on immune-related toxicities and infusion-related reactions, given the unique design of QH101 that avoids T cell exhaustion from overactivation.

In addition to safety monitoring, the study will collect serial peripheral blood samples at predefined time points to assess the in vivo persistence, activation status, and tissue homing potential of QH101. Correlative studies will be conducted to explore the interaction between QH101 and the tumor microenvironment, especially the binding efficiency of BTN protein-specific binding elements to tumor-expressed BTN2A1/BTN3A1, as well as the relationship between the in vivo dynamics of QH101 and preliminary antitumor activity.

The primary goal of this early clinical research is to confirm the safety profile of QH101, determine the feasible dose range for subsequent studies, and obtain preliminary evidence of its biological activity, including in vivo persistence and tumor-targeting capability. The findings from this study will lay a solid foundation for the further clinical development of QH101, providing critical insights into its potential as a novel cellular therapy for advanced solid tumors.

Inclusion Criteria:

1. Age ≥18 years;

2. ECOG ≤2 or KPS ≥60;

3. Life expectancy ≥8 weeks as assessed by the investigator;

4. Pathologically and/or histologically confirmed malignant tumors with brain, meningeal, and spinal cord metastases that have failed standard therapy or lack standard treatment options may be considered for enrollment;

5. Intracranial metastases must meet the following characteristics:

   Unresectable by craniotomy for solitary/focal (≤3 lesions)/multiple (>3 lesions) intracranial metastases; or inoperable leptomeningeal or spinal cord metastases; Inclusion Criteria Intracranial lesions that progressed after standard treatment, including whole-brain radiotherapy/stereotactic radiosurgery (WBRT/SRS), and are not suitable for repeat radiotherapy;

6. For brain/spinal cord parenchymal metastases, contrast-enhanced MRI must show at least one measurable lesion (according to iRANO criteria); for patients with meningeal lesions only, those deemed likely to benefit from this study by investigator judgment may also be considered for inclusion (efficacy assessed using RANO-LM criteria);

7. Basic normal bone marrow reserve function and normal hepatic and renal function (laboratory tests must meet the following criteria prior to first QH101 administration):

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

8. Pregnancy test must be negative for women of childbearing potential; both male and female subjects must agree to use effective contraception during treatment and for 1 year thereafter;

9. Ability to understand trial requirements and procedures, and willingness to participate in the clinical study as required;

10. Signing of the trial informed consent form.

Exclusion Criteria:

1. Received central nervous system-directed radiation within 7 days prior to the first infusion of QH101;
2. Patients with hematologic malignancies (such as lymphoma, leukemia, etc.) with central nervous system metastases;
3. Patients with metastases in the brainstem and high cervical spinal cord, including midbrain, pons, medulla oblongata, and C1/2 segments of the cervical spinal cord;
4. Patients with significant mass effect from intracranial lesions and signs of increased intracranial pressure (such as severe headache, projectile vomiting, papilledema, altered consciousness, or imaging showing significant edema, midline shift ≥1 cm, compression of peribrain cisterns such as suprasellar cistern, quadrigeminal cistern, interpeduncular cistern, or ambient cistern);
5. Patients with primary or secondary epilepsy/epileptic syndrome that is difficult to control with medication;
6. Uncontrolled comorbidities, including but not limited to: ongoing or active infections, symptomatic congestive heart failure, unstable angina, arrhythmias, or psychiatric/social conditions limiting patient compliance with study requirements;
7. Known psychiatric disorders or substance abuse disorders that may affect compliance with trial requirements;
8. Currently receiving any other investigational treatments;
9. Diagnosed with an immunodeficiency;
10. Patients with active infections requiring systemic treatment;
11. Inability to undergo magnetic resonance imaging (MRI);
12. Severe cardiovascular damage: history of New York Heart Association (NYHA) class II or higher congestive heart failure, unstable angina, myocardial infarction or stroke within 6 months after first dosing, or clinically significant arrhythmias requiring treatment at screening;
13. Allergic to immunotherapy or related cellular therapies;
14. Previously received CAR-T or other cellular immunotherapies;
15. Other reasons that the investigator considers make the patient unsuitable for participation in this study.