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HRYZ-T101 Injection for HPV18 Positive Solid Tumor

Primary Purpose

Cervical Cancer, Head and Neck Squamous Cell Carcinoma, Carcinoma of Vagina

Status
Not yet recruiting
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
HRYZ-T101 Injection
Fludarabine + Cyclophosphamide
Sponsored by
HRYZ Biotech Co.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cervical Cancer

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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: Leukocytes≥3.0 x 10^9/L; blood platelets ≥75 x 10^9/L; hemoglobin≥85g/L; Absolute lymphocyte count≥0.8 x 10^9/L Serum albumin ≥ 30g/L; total bilirubin≤1.5×ULN; ALT/AST≤3×ULN or ≤5×ULN for liver metastases; Creatinine clearance ≥50mL/min; or serum creatinine ≤1.5×ULN; INR≤1.5×ULN; APTT≤1.5×ULN; LVEF≥50%; 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.

Sites / Locations

  • Fudan University Shanghai Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

HRYZ-T101 Injection

Arm Description

Patients will undergo lymphocytapheresis, then treatment with HRYZ-T101 TCR-T cells.

Outcomes

Primary Outcome Measures

DLT
Dose-limiting toxicity
Adverse events and serious adverse events
Incidence of adverse events and serious adverse events

Secondary Outcome Measures

Objective Response Rate(ORR)
The percentage of subjects with PR or CR assessed by RECIST 1.1.
Disease Control Rate (DCR)
The percentage of subjects with a confirmed CR, PR, or stable disease (SD) assessed by RECIST 1.1.
Duration of response (DoR)
Subjects who show a confirmed CR or PR as assessed by RECIST 1.1.
Time to response (TTR)
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)
The length of time from enrollment until the time of progression of disease.
Overall Survival (OS)
The interval of time between the date of T-cell infusion and the date of death.
Duration of TCR T cells in-vivo persistence
Blood samples were collected to measure persistence of infused HRYZ-T101.
Concentration of Cytokines (IL-2、IL-6、IL-10、TNFα、IFNγ)
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.

Full Information

First Posted
July 5, 2023
Last Updated
July 17, 2023
Sponsor
HRYZ Biotech Co.
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1. Study Identification

Unique Protocol Identification Number
NCT05952947
Brief Title
HRYZ-T101 Injection for HPV18 Positive Solid Tumor
Official Title
A Multicenter, Single Arm, Open Label, Phase I Clinical Study to Evaluate the Safety, Tolerability and Efficacy of HRYZ-T101 Injection for HPV18 Positive Solid Tumor
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
October 2023 (Anticipated)
Primary Completion Date
December 2027 (Anticipated)
Study Completion Date
February 2028 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
HRYZ Biotech Co.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cervical Cancer, Head and Neck Squamous Cell Carcinoma, Carcinoma of Vagina, Carcinoma of Penis, Anal Cancer, Carcinoma of Vulva

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
32 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
HRYZ-T101 Injection
Arm Type
Experimental
Arm Description
Patients will undergo lymphocytapheresis, then treatment with HRYZ-T101 TCR-T cells.
Intervention Type
Biological
Intervention Name(s)
HRYZ-T101 Injection
Intervention Description
On day 1, the TCR-T cells will be administered intravenously.
Intervention Type
Drug
Intervention Name(s)
Fludarabine + Cyclophosphamide
Intervention Description
Fludarabine: 25mg/m²/day×3days; Cyclophosphamide: 250mg/m²/day×3 days
Primary Outcome Measure Information:
Title
DLT
Description
Dose-limiting toxicity
Time Frame
28 days
Title
Adverse events and serious adverse events
Description
Incidence of adverse events and serious adverse events
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Objective Response Rate(ORR)
Description
The percentage of subjects with PR or CR assessed by RECIST 1.1.
Time Frame
2 years
Title
Disease Control Rate (DCR)
Description
The percentage of subjects with a confirmed CR, PR, or stable disease (SD) assessed by RECIST 1.1.
Time Frame
2 years
Title
Duration of response (DoR)
Description
Subjects who show a confirmed CR or PR as assessed by RECIST 1.1.
Time Frame
2 years
Title
Time to response (TTR)
Description
Time from date of T-cell administration to first documented evidence of confirmed (CR or PR) as assessed by RECIST 1.1.
Time Frame
2 years
Title
Progression-Free Survival(PFS)
Description
The length of time from enrollment until the time of progression of disease.
Time Frame
2 years
Title
Overall Survival (OS)
Description
The interval of time between the date of T-cell infusion and the date of death.
Time Frame
2 years
Title
Duration of TCR T cells in-vivo persistence
Description
Blood samples were collected to measure persistence of infused HRYZ-T101.
Time Frame
2 years
Title
Concentration of Cytokines (IL-2、IL-6、IL-10、TNFα、IFNγ)
Description
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.
Time Frame
2 years
Other Pre-specified Outcome Measures:
Title
Number of Subjects with positive anti-drug antibodies (ADA)
Description
Serum samples will be collected to analyze for the presence of ADAs using validated immunoassays.
Time Frame
2 years
Title
Number of subjects with replication competent lentivirus (RCL)
Description
RCL exposure will be assessed by polymerase chain reaction (PCR) based assay.
Time Frame
2 years
Title
T cell subgroup in peripheral blood
Description
Collect blood samples and analyze for T cell subgroup by flow cytometry at specified intervals before and after treatment with HRYZ-T101.
Time Frame
2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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: Leukocytes≥3.0 x 10^9/L; blood platelets ≥75 x 10^9/L; hemoglobin≥85g/L; Absolute lymphocyte count≥0.8 x 10^9/L Serum albumin ≥ 30g/L; total bilirubin≤1.5×ULN; ALT/AST≤3×ULN or ≤5×ULN for liver metastases; Creatinine clearance ≥50mL/min; or serum creatinine ≤1.5×ULN; INR≤1.5×ULN; APTT≤1.5×ULN; LVEF≥50%; 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Xuemin Rao
Phone
021-61049928
Email
raoxuemin@shhryz.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Xiaohua Wu, Doctor
Organizational Affiliation
Fudan University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Jian Zhang, Doctor
Organizational Affiliation
Fudan University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Fudan University Shanghai Cancer Center
City
Shanghai
State/Province
Shanghai
Country
China

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

HRYZ-T101 Injection for HPV18 Positive Solid Tumor

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