Anal Cancer, Carcinoma of Penis, Carcinoma of Vagina, Carcinoma of Vulva, Cervical Cancer, Head and Neck Squamous Cell Carcinoma
Conditions
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.
Interventions
BIOLOGICALHRYZ-T101 Injection
On day 1, the TCR-T cells will be administered intravenously.
Fludarabine: 25mg/m²/day×3days; Cyclophosphamide: 250mg/m²/day×3 days
Sponsors
HRYZ Biotech Co.
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
* 1\. The patient must be willing to sign the informed consent form. * 2\. Age ≥18 years and ≤75 years. * 3\. Metastatic or recurrent solid tumors with confirmed HPV18 infection based on TNM & FIGO staged histopathological investigation. . * 4\. Subjects who have failed anti-tumor treatment in the past and lack effective treatment options. * 5\. HPV18 positive and HLA-DRB1\*0901 allele. * 6\. ECOG performance status ≤1. * 7\. Estimated life expectancy ≥ 3 months. * 8\. Patients must have at least one measurable lesion defined by RECIST 1.1. * 9\. Patients with any organ dysfunction as defined below: 1. Leukocytes≥3.0 x 10\^9/L; 2. blood platelets ≥75 x 10\^9/L; 3. hemoglobin≥85g/L; 4. Absolute lymphocyte count≥0.8 x 10\^9/L 5. Serum albumin ≥ 30g/L; 6. total bilirubin≤1.5×ULN; ALT/AST≤3×ULN or ≤5×ULN for liver metastases; 7. Creatinine clearance ≥50mL/min; or serum creatinine ≤1.5×ULN; 8. INR≤1.5×ULN; APTT≤1.5×ULN; 9. LVEF≥50%; 10. SpO2≥92%. * 10\. 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
* 1\. 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. * 2\. 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. * 3\. Have received any investigational drug within 4 weeks before apheresis, or have participated in another clinical study at the same time. * 4\. Have received any cell therapy products before. * 5\. Those who have undergone major surgery within 4 weeks before apheresis, or minor surgery within 2 weeks before apheresis. * 6\. Toxicity of previous treatment has not been mitigated or ≤ Grade 1 before apheresis. * 7\. Have received live attenuated vaccine or adenovirus vector vaccine within 4 weeks before apheresis. * 8\. Have central nervous system metastasis with symptoms. * 9\. Subjects with clinical cardiac symptoms or diseases that cannot be well controlled. * 10\. Subjects with serious or uncontrolled systemic disease or any unstable systemic disease. * 11\. Subjects with active infection requiring systemic treatment with anti-infective drugs within 2 weeks before apheresis. * 12\. Subjects have any active autoimmune disease or history of autoimmune disease. * 13\. Have received immunosuppressive agents, or systemic corticosteroids, immunomodulators within 2 weeks before apheresis. * 14\. 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. * 15\. Subjects with history of thromboembolism ≥ Grade 3 within 6 months before apheresis, or is receiving thrombolytic or anticoagulant for high-risk of thromboembolism. * 16\. Known HIV or syphilis infection, and/or active hepatitis B virus or hepatitis C virus infection. * 17\. Organ transplanters and allogeneic cell transplanters. * 18\. Subjects with active pulmonary tuberculosis infection within 1 year or have not received treatment at least 1 year before apheresis. * 19\. Pregnant or lactating female, or those whose HCG test is positive before enrollment. * 20\. According to the judgment of the researcher, those who are not suitable for the group, such as poor compliance.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| DLT | 28 days | Dose-limiting toxicity |
| Adverse events and serious adverse events | 2 years | Incidence of adverse events and serious adverse events |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| Objective Response Rate（ORR） | 2 years | The percentage of subjects with PR or CR assessed by RECIST 1.1. |
| 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. |
| Progression-Free Survival（PFS） | 2 years | The length of time from enrollment until the time of progression of disease. |
Other
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| Number of subjects with replication competent lentivirus (RCL) | 2 years | RCL exposure will be assessed by polymerase chain reaction (PCR) based assay. |
Countries
China
Contacts
Primary ContactXuemin Rao
Outcome results
None listed