HRYZ-T101 TCR-T Cell for HPV-18 Positive Advanced Solid Tumor
Study Details
Study Description
Brief Summary
A single center, open, single arm dose escalation phase I study to evaluate the safety, tolerability, and efficacy of HRYZ-T101 TCR-T cell for HPV18 positive advanced solid tumor. The study will investigate DLT 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 TCR-T cell therapy Patients will undergo lymphocytapheresis, then treatment with TCR-T cell. |
Drug: Fludarabine + Cyclophosphamide
Fludarabine: 25mg/m²/day×3days; Cyclophosphamide: 250mg/m²/day×3 days
Biological: HRYZ-T101 TCR-T Cell
On day 1, the TCR-T cells will be administered one time.
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Outcome Measures
Primary Outcome Measures
- DLT [28 days]
Dose-limiting toxicity
- Incidence of treatment related AEs, AEs of special interest and serious adverse events (SAEs). [2 years]
Assessed by CTCAE V5.0
Secondary Outcome Measures
- Objective Response Rate(ORR) [2 years]
The percentage of subjects with PR or CR assessed by RECIST 1.1.
- Overall Survival (OS) [2 years]
From enrollment to death of patients.
- Duration of Response(DOR) [2 years]
The length of time from the first appearance of a treatment response to the first occurrence of progressive disease or recurrence.
- Progression-Free Survival(PFS) [2 years]
The length of time from enrollment until the time of progression of disease.
- Duration of TCR T cells in-vivo persistence [Up to 2 years]
Blood samples were collected to measure persistence of infused 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 ≤70 years.
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Histologically-confirmed advanced metastatic or recurrent solid tumors with confirmed HPV18 infection and HLA-DRB1*09:01 allele.
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Subjects who have failed at least first-line treatment in the past and lack effective treatment options.
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ECOG performance status of 0-1.
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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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Subjects with potential fertility must agree to use effective contraceptive methods during the whole trials period and at least 6 months after receiving HRYZ-T101 cell transfusion treatment.
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Patients with any organ dysfunction as defined below:
- Leukocytes≥3.0 x 109/L; 2) absolute neutrophil count ≤1.5 x 109/L; 3) blood platelets ≥75 x 10^9/L; 4) hemoglobin≥90g/L; 5) Serum albumin ≥ 3.0g/dL; 6) total bilirubin≤1.5×ULN; ALT/AST≤2.5×ULN; 7) Creatinine clearance ≥50mL/min; 8) INR≤1.5×ULN; APTT≤1.5×ULN; 9) LVEF≥50%; 10) SpO2≥92%.
Exclusion Criteria:
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Organ transplanters and allogeneic cell transplanters.
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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 major surgery within 4 weeks before enrollment, and those who have received conventional chemotherapy, large-area radiotherapy, targeted therapy, endocrine therapy, immunotherapy or biological therapy, and Chinese herbal medicine and other anti-tumor treatment.
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Have received live attenuated vaccine within 4 weeks before enrollment.
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Subjects with clinical cardiac symptoms or diseases that cannot be well controlled.
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The subject has active infection or fever more than 38.5 degrees of unknown cause during screening and before cell transfusion.
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Subjects have any active autoimmune disease or history of autoimmune disease.
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Subjects with other malignant tumors.
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Patients with central nervous system metastasis.
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Active, uncontrolled bacterial or fungal infection requiring systemic treatment.
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Known HIV or syphilis infection, and/or active hepatitis B virus or hepatitis C virus infection.
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It is planned to use immunosuppressive agents, or systemic corticosteroids, immunomodulators.
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Have received any investigational drug within 4 weeks before enrollment, or have participated in another clinical study at the same time.
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Pregnant or lactating subjects, or those who are unwilling to contraception during the test.
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Known uncontrolled diabetes, pulmonary fibrosis, interstitial lung disease, acute lung disease or liver failure.
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Other serious organic diseases and mental disorders.
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Have received any gene therapy products before.
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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 | 200120 |
Sponsors and Collaborators
- SYZ Cell Therapy Co..
Investigators
- Principal Investigator: Jian Zhang, Doctor, Fudan University
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- HRYZ-T101-1002