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HRYZ-T101 TCR-T Cell for HPV-18 Positive Advanced Solid Tumor

Primary Purpose

Cervical Cancer, Head and Neck Squamous Cell Carcinoma, Oropharyngeal Cancer

Status
Recruiting
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
Fludarabine + Cyclophosphamide
HRYZ-T101 TCR-T Cell
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 - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: The patient must be willing to sign the informed consent form. Age ≥18 years and ≤70 years. Histologically-confirmed advanced metastatic or recurrent solid tumors with confirmed HPV18 infection and HLA-DRB1*09:01 allele. Subjects who have failed at least first-line treatment in the past and lack effective treatment options. ECOG performance status of 0-1. Estimated life expectancy ≥ 3 months. Patients must have at least one measurable lesion defined by RECIST 1.1. 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. Patients with any organ dysfunction as defined below: 1) Leukocytes≥3.0 x 10^9/L; 2) absolute neutrophil count ≤1.5 x 10^9/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: Organ transplanters and allogeneic cell transplanters. 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. 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. Have received live attenuated vaccine within 4 weeks before enrollment. Subjects with clinical cardiac symptoms or diseases that cannot be well controlled. The subject has active infection or fever more than 38.5 degrees of unknown cause during screening and before cell transfusion. Subjects have any active autoimmune disease or history of autoimmune disease. Subjects with other malignant tumors. Patients with central nervous system metastasis. Active, uncontrolled bacterial or fungal infection requiring systemic treatment. Known HIV or syphilis infection, and/or active hepatitis B virus or hepatitis C virus infection. It is planned to use immunosuppressive agents, or systemic corticosteroids, immunomodulators. Have received any investigational drug within 4 weeks before enrollment, or have participated in another clinical study at the same time. Pregnant or lactating subjects, or those who are unwilling to contraception during the test. Known uncontrolled diabetes, pulmonary fibrosis, interstitial lung disease, acute lung disease or liver failure. Other serious organic diseases and mental disorders. Have received any gene therapy products before. 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 CenterRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

HRYZ-T101 TCR-T cell therapy

Arm Description

Patients will undergo lymphocytapheresis, then treatment with TCR-T cell.

Outcomes

Primary Outcome Measures

DLT
Dose-limiting toxicity
Incidence of treatment related AEs, AEs of special interest and serious adverse events (SAEs).
Assessed by CTCAE V5.0

Secondary Outcome Measures

Objective Response Rate(ORR)
The percentage of subjects with PR or CR assessed by RECIST 1.1.
Overall Survival (OS)
From enrollment to death of patients.
Duration of Response(DOR)
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)
The length of time from enrollment until the time of progression of disease.
Duration of TCR T cells in-vivo persistence
Blood samples were collected to measure persistence of infused HRYZ-T101.

Full Information

First Posted
March 14, 2023
Last Updated
October 19, 2023
Sponsor
HRYZ Biotech Co.
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1. Study Identification

Unique Protocol Identification Number
NCT05787535
Brief Title
HRYZ-T101 TCR-T Cell for HPV-18 Positive Advanced Solid Tumor
Official Title
A Phase I Study to Evaluate the Safety, Tolerance and Efficacy of HRYZ-T101 TCR-T Cell for HPV18 Positive Advanced Solid Tumor
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 21, 2023 (Actual)
Primary Completion Date
February 2025 (Anticipated)
Study Completion Date
September 2025 (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 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.

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, Oropharyngeal Cancer, Vagina Tumor, Carcinoma of Penis, Anal Carcinoma, 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
17 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
HRYZ-T101 TCR-T cell therapy
Arm Type
Experimental
Arm Description
Patients will undergo lymphocytapheresis, then treatment with TCR-T cell.
Intervention Type
Drug
Intervention Name(s)
Fludarabine + Cyclophosphamide
Intervention Description
Fludarabine: 25mg/m²/day×3days; Cyclophosphamide: 250mg/m²/day×3 days
Intervention Type
Biological
Intervention Name(s)
HRYZ-T101 TCR-T Cell
Intervention Description
On day 1, the TCR-T cells will be administered one time.
Primary Outcome Measure Information:
Title
DLT
Description
Dose-limiting toxicity
Time Frame
28 days
Title
Incidence of treatment related AEs, AEs of special interest and serious adverse events (SAEs).
Description
Assessed by CTCAE V5.0
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
Overall Survival (OS)
Description
From enrollment to death of patients.
Time Frame
2 years
Title
Duration of Response(DOR)
Description
The length of time from the first appearance of a treatment response to the first occurrence of progressive disease or recurrence.
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
Duration of TCR T cells in-vivo persistence
Description
Blood samples were collected to measure persistence of infused HRYZ-T101.
Time Frame
Up to 2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: The patient must be willing to sign the informed consent form. Age ≥18 years and ≤70 years. Histologically-confirmed advanced metastatic or recurrent solid tumors with confirmed HPV18 infection and HLA-DRB1*09:01 allele. Subjects who have failed at least first-line treatment in the past and lack effective treatment options. ECOG performance status of 0-1. Estimated life expectancy ≥ 3 months. Patients must have at least one measurable lesion defined by RECIST 1.1. 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. Patients with any organ dysfunction as defined below: 1) Leukocytes≥3.0 x 10^9/L; 2) absolute neutrophil count ≤1.5 x 10^9/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: Organ transplanters and allogeneic cell transplanters. 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. 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. Have received live attenuated vaccine within 4 weeks before enrollment. Subjects with clinical cardiac symptoms or diseases that cannot be well controlled. The subject has active infection or fever more than 38.5 degrees of unknown cause during screening and before cell transfusion. Subjects have any active autoimmune disease or history of autoimmune disease. Subjects with other malignant tumors. Patients with central nervous system metastasis. Active, uncontrolled bacterial or fungal infection requiring systemic treatment. Known HIV or syphilis infection, and/or active hepatitis B virus or hepatitis C virus infection. It is planned to use immunosuppressive agents, or systemic corticosteroids, immunomodulators. Have received any investigational drug within 4 weeks before enrollment, or have participated in another clinical study at the same time. Pregnant or lactating subjects, or those who are unwilling to contraception during the test. Known uncontrolled diabetes, pulmonary fibrosis, interstitial lung disease, acute lung disease or liver failure. Other serious organic diseases and mental disorders. Have received any gene therapy products before. 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
First Name & Middle Initial & Last Name or Official Title & Degree
Guoping Chen
Email
chenguoping@shhryz.com
Overall Study Officials:
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
ZIP/Postal Code
200120
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Guoping Chen
Email
chenguoping@shhryz.com
First Name & Middle Initial & Last Name & Degree
Jian Zhang, Doctor

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

HRYZ-T101 TCR-T Cell for HPV-18 Positive Advanced Solid Tumor

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