HRYZ-T101 Injection for HPV18 Positive Solid Tumor
Study Details
Study Description
Brief Summary
A multicenter, open label, single arm dose escalation phase I study to evaluate the safety, tolerability, and efficacy of HRYZ-T101 injection for HPV18 positive solid tumor. The study will investigate RP2D of HRYZ-T101 TCR-T cell injection.
Condition or Disease | Intervention/Treatment | Phase |
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Phase 1 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: HRYZ-T101 Injection Patients will undergo lymphocytapheresis, then treatment with HRYZ-T101 TCR-T cells. |
Biological: HRYZ-T101 Injection
On day 1, the TCR-T cells will be administered intravenously.
Drug: Fludarabine + Cyclophosphamide
Fludarabine: 25mg/m²/day×3days; Cyclophosphamide: 250mg/m²/day×3 days
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Outcome Measures
Primary Outcome Measures
- DLT [28 days]
Dose-limiting toxicity
- Adverse events and serious adverse events [2 years]
Incidence of adverse events and serious adverse events
Secondary Outcome Measures
- Objective Response Rate(ORR) [2 years]
The percentage of subjects with PR or CR assessed by RECIST 1.1.
- Disease Control Rate (DCR) [2 years]
The percentage of subjects with a confirmed CR, PR, or stable disease (SD) assessed by RECIST 1.1.
- Duration of response (DoR) [2 years]
Subjects who show a confirmed CR or PR as assessed by RECIST 1.1.
- Time to response (TTR) [2 years]
Time from date of T-cell administration to first documented evidence of confirmed (CR or PR) as assessed by RECIST 1.1.
- Progression-Free Survival(PFS) [2 years]
The length of time from enrollment until the time of progression of disease.
- Overall Survival (OS) [2 years]
The interval of time between the date of T-cell infusion and the date of death.
- Duration of TCR T cells in-vivo persistence [2 years]
Blood samples were collected to measure persistence of infused HRYZ-T101.
- Concentration of Cytokines (IL-2、IL-6、IL-10、TNFα、IFNγ) [2 years]
Collect blood samples and analyze for presence of cytokines (IL-2、IL-6、IL-10、TNFα、IFNγ) at specified intervals before and after treatment with HRYZ-T101.
Other Outcome Measures
- Number of Subjects with positive anti-drug antibodies (ADA) [2 years]
Serum samples will be collected to analyze for the presence of ADAs using validated immunoassays.
- Number of subjects with replication competent lentivirus (RCL) [2 years]
RCL exposure will be assessed by polymerase chain reaction (PCR) based assay.
- T cell subgroup in peripheral blood [2 years]
Collect blood samples and analyze for T cell subgroup by flow cytometry at specified intervals before and after treatment with HRYZ-T101.
Eligibility Criteria
Criteria
Inclusion Criteria:
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- The patient must be willing to sign the informed consent form.
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- Age ≥18 years and ≤75 years.
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- Metastatic or recurrent solid tumors with confirmed HPV18 infection based on TNM & FIGO staged histopathological investigation. .
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- Subjects who have failed anti-tumor treatment in the past and lack effective treatment options.
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- HPV18 positive and HLA-DRB1*0901 allele.
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- ECOG performance status ≤1.
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- Estimated life expectancy ≥ 3 months.
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- Patients must have at least one measurable lesion defined by RECIST 1.1.
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- Patients with any organ dysfunction as defined below:
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Leukocytes≥3.0 x 10^9/L;
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blood platelets ≥75 x 10^9/L;
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hemoglobin≥85g/L;
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Absolute lymphocyte count≥0.8 x 10^9/L
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Serum albumin ≥ 30g/L;
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total bilirubin≤1.5×ULN; ALT/AST≤3×ULN or ≤5×ULN for liver metastases;
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Creatinine clearance ≥50mL/min; or serum creatinine ≤1.5×ULN;
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INR≤1.5×ULN; APTT≤1.5×ULN;
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LVEF≥50%;
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SpO2≥92%.
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- Subjects with potential fertility must agree to use effective contraceptive methods during the whole trials period and at least 1 year after receiving HRYZ-T101 cell transfusion treatment. HCG test for female with potential fertility must be negative within 7 days before apheresis.
Exclusion Criteria:
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- Have a history of hypersensitivity to cyclophosphamide or fludarabine, and it is known that any ingredient used in the treatment of this study will produce allergic reactions.
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- Those who have undergone systemic anti-tumor treatment within 4 weeks before apheresis, including who have received conventional chemotherapy, large-area radiotherapy, targeted therapy, immunotherapy or biological therapy, and other anti-tumor treatment. Have received small molecule targeted drugs and oral fluorouracils or Chinese herbal medicine within 2 weeks before apheresis.
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- Have received any investigational drug within 4 weeks before apheresis, or have participated in another clinical study at the same time.
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- Have received any cell therapy products before.
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- Those who have undergone major surgery within 4 weeks before apheresis, or minor surgery within 2 weeks before apheresis.
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- Toxicity of previous treatment has not been mitigated or ≤ Grade 1 before apheresis.
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- Have received live attenuated vaccine or adenovirus vector vaccine within 4 weeks before apheresis.
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- Have central nervous system metastasis with symptoms.
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- Subjects with clinical cardiac symptoms or diseases that cannot be well controlled.
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- Subjects with serious or uncontrolled systemic disease or any unstable systemic disease.
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- Subjects with active infection requiring systemic treatment with anti-infective drugs within 2 weeks before apheresis.
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- Subjects have any active autoimmune disease or history of autoimmune disease.
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- Have received immunosuppressive agents, or systemic corticosteroids, immunomodulators within 2 weeks before apheresis.
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- Subjects with other malignant tumors. Except for: (1) Carcinoma in situ with curative treatment and no evidence of recurrence for at least 2 years; (2) the primary malignant tumor has been completely resected and achieved CR for ≥ 2 years.
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- Subjects with history of thromboembolism ≥ Grade 3 within 6 months before apheresis, or is receiving thrombolytic or anticoagulant for high-risk of thromboembolism.
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- Known HIV or syphilis infection, and/or active hepatitis B virus or hepatitis C virus infection.
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- Organ transplanters and allogeneic cell transplanters.
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- Subjects with active pulmonary tuberculosis infection within 1 year or have not received treatment at least 1 year before apheresis.
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- Pregnant or lactating female, or those whose HCG test is positive before enrollment.
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- According to the judgment of the researcher, those who are not suitable for the group, such as poor compliance.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | Fudan University Shanghai Cancer Center | Shanghai | Shanghai | China |
Sponsors and Collaborators
- SYZ Cell Therapy Co..
Investigators
- Principal Investigator: Xiaohua Wu, Doctor, Fudan University
- Principal Investigator: Jian Zhang, Doctor, Fudan University
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- H-T01-C2001