Hematologic Malignancy, Solid Tumor
Conditions
Brief summary
QH101 is an allogeneic TCR-enhanced Vδ2 T cell therapeutic product. By introducing a specific BTN protein-binding moiety onto the cell surface, it leverages the inherent tumoricidal capacity of Vδ2 T cells and enhances their recognition of BTN proteins, thereby improving the killing efficiency against tumor cells. Meanwhile, QH101 does not express co-stimulatory signaling domains or the CD3ζ domain, which avoids cell exhaustion caused by excessive activation and effectively improves the persistence of cells in vivo. This study is an open, prospective, open-label, phase I/II clinical trial designed to evaluate the safety and efficacy of QH101 Cell Injection in subjects with relapsed/refractory hematologic malignancies and advanced solid tumors.
Interventions
BIOLOGICALQH101 Cell Injection
Biological: QH101 cell Following lymphodepletion with chemotherapy (cyclophosphamide and fludarabine) patients will be treated with dose escalation (3+3) : dose 1 (1×10\^7 CAR+cells) ,dose 2 (3× 10\^7 CAR+cells)，dose 3 (6× 10\^7 CAR+cells). After the MTD and/or RP2D is determined in the dose escalation phase, a cohort expansion study may be initiated upon the investigator's decision. Enrolled subjects will receive QH101 infusion following lymphodepleting conditioning at the MTD and/or RP2D dose level established during the dose escalation phase.
Eligible subjects will undergo lymphodepletion chemotherapy 5 to 3 days prior to cell infusion. The recommended lymphodepletion regimen comprises cyclophosphamide (500-1000 mg/m² administered 3 days).
Eligible subjects will receive lymphodepletion chemotherapy 5 to 3 days prior to cell infusion. The recommended lymphodepletion regimen comprises fludarabine (30-50 mg/m² administered 3 days).
Sponsors
Chinese PLA General Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Age 18-75 (inclusive). * Expected survival time ≥ 3 months. * Meets current clinical diagnostic criteria with a confirmed diagnosis of a malignant hematologic tumor or solid tumor, and has failed standard therapy (for solid tumors, at least one evaluable lesion according to RECIST v1.1 is required). * Adequate bone marrow reserve and essentially normal liver and kidney function (laboratory tests must meet the following criteria prior to the first QH101 treatment): * Hematology: White Blood Cell Count (WBC) ≥ 3×10⁹/L, Lymphocyte Count (LY) ≥ 0.8×10⁹/L, Hemoglobin (Hb) ≥ 80 g/L, Platelets (PLT) ≥ 75×10⁹/L. * Liver: ALT ≤ 3 × ULN; AST ≤ 3 × ULN; Total Bilirubin ≤ 3.0 × ULN. * Kidney: Serum Creatinine ≤ 1.5 × ULN. * Cardiac: Left Ventricular Ejection Fraction (LVEF) ≥ 50% as measured by echocardiogram. * Pulmonary: Normal oxygen saturation without supplemental oxygen. * Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0-1. * A negative pregnancy test is required for women of childbearing potential. Both male and female subjects must agree to use effective contraception during the treatment period and for 1 year thereafter. * Able to understand the trial requirements and is willing to participate in the clinical study as required. * Voluntarily signs the informed consent form for the clinical trial.
Exclusion criteria
* Known history of allergy, hypersensitivity, intolerance, or contraindication to QH101 or any components of the study drugs (including fludarabine and cyclophosphamide). * Continuous use of immunosuppressants within 1 month prior to QH101 infusion. * History of cerebrovascular accident or seizure within 6 months prior to signing the informed consent. * Symptomatic brain metastases. * Known psychiatric or substance abuse disorders that would compromise compliance with study requirements. * Positive for Hepatitis B surface antigen (HBsAg) or Hepatitis B core antibody (HBcAb) with detectable Hepatitis B virus (HBV) DNA levels outside the normal reference range; positive for Hepatitis C virus (HCV) antibody with detectable HCV RNA; positive for Human Immunodeficiency Virus (HIV) antibody; positive for syphilis. * Severe cardiac disease, including but not limited to unstable angina, myocardial infarction (within 6 months prior to screening), congestive heart failure (NYHA Class ≥ III), and severe arrhythmia. * Active or uncontrolled infection requiring systemic therapy (except for mild urogenital and upper respiratory tract infections). * Has not recovered from acute toxic effects of prior therapy (i.e., persisting hematological or organ toxicity ≥ Grade 2 related to prior therapy, excluding abnormalities associated with the study disease and its history). * Diagnosed with immunodeficiency. * Active infection requiring systemic treatment. * Female subjects of childbearing potential planning pregnancy within 2 years after cell infusion; or male subjects whose partners are planning pregnancy within 2 years after cell infusion. * Participation in another investigational drug clinical study within 1 month prior to screening. * Last anti-tumor therapy administered less than 5 half-lives of the drug prior to planned QH101 infusion. * Any other condition deemed by the investigator to make the subject unsuitable for participation in this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Event | 12 months | AE is defined as any adverse medical event from the date of leukapheresis to 12 months after QH101 cell infusion. Among them, cytokine release syndrome (CRS) 、 immune cell-associated neurotoxicity syndrome (ICANS) 、 graft-versushost disease (GVHD) are excluded . Other AEs were graded according to the regulatory agency's Medical Dictionary for Regulatory Activities (MedDRA) and common terminology criteria for adverse events (CTCAE) v5.0 |
| DLTs | 28 days after cell infusion | DLT was defined as QH101-related events with onset within first 28 days following infusion |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PK(Pharmacokinetics):Number and Copy Number of QH101 cells | 12 months | Number and copy number of QH101 cells were assessed by number in peripheral blood. Blood samples were collected before and one year after cell infusion (until QH101 cells were not detected for two consecutive times) to detect the number and copy number of QH101 cells, and to evaluate the pharmacokinetics of QH101. |
| PD(Pharmacodynamics):changes over time | 12 months | To monitor changes over time in the cytokines mainly include interleukin-2 (IL-2 ), IL-4,IL-6, interferon-γ（IFN-γ), Tumor Necrosis Factor-alpha (TNF-α). |
| Objective Response Rate | 12 months after cell infusion | The incidence of complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD) are the response to treatment assessed by investigators. |
| Overall Survival(OS) | 12 months | OS is defined as the time from QH101 infusion to the date of death. |
| Progression Free Survival (PFS) | 12 months | PFS is defined as the time from the QH101 infusion date to the date of disease progression assessed by investigators. |
Countries
China
Contacts
CONTACTWeidong Han
Outcome results
None listed