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

Phase 1

Recruiting

• Conditions: Oropharyngeal Cancer; Anal Carcinoma; Head and Neck Squamous Cell Carcinoma; Carcinoma of Penis; Cervical Cancer; Vagina Tumor; Carcinoma of Vulva
• Interventions: Drug: Fludarabine + Cyclophosphamide; Biological: HRYZ-T101 TCR-T Cell

• Registration Number: NCT05787535
• Lead Sponsor: HRYZ Biotech Co.

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.

Detailed Description

Not available

Study Timeline

• Status Verified: 2023-03
• Study First Submitted: 2023-03-14
• Study Start: 2023-03-21
• Study First Submitted QC: 2023-03-27
• Study First Posted: 2023-03-28
• Last Update Submitted: 2024-01-31
• Last Update Posted: 2024-02-02
• Primary Completion: 2025-02
• Study Completion: 2025-09

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 17

Inclusion Criteria

1. The patient must be willing to sign the informed consent form.
2. Age ≥18 years and ≤70 years.
3. Histologically-confirmed advanced metastatic or recurrent solid tumors with confirmed HPV18 infection and HLA-DRB1*09:01 allele.
4. Subjects who have failed at least first-line treatment in the past and lack effective treatment options.
5. ECOG performance status of 0-1.
6. Estimated life expectancy ≥ 3 months.
7. Patients must have at least one measurable lesion defined by RECIST 1.1.
8. 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.
9. 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

1. Organ transplanters and allogeneic cell transplanters.
2. 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.
3. 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.
4. Have received live attenuated vaccine within 4 weeks before enrollment.
5. Subjects with clinical cardiac symptoms or diseases that cannot be well controlled.
6. The subject has active infection or fever more than 38.5 degrees of unknown cause during screening and before cell transfusion.
7. Subjects have any active autoimmune disease or history of autoimmune disease.
8. Subjects with other malignant tumors.
9. Patients with central nervous system metastasis.
10. Active, uncontrolled bacterial or fungal infection requiring systemic treatment.
11. Known HIV or syphilis infection, and/or active hepatitis B virus or hepatitis C virus infection.
12. It is planned to use immunosuppressive agents, or systemic corticosteroids, immunomodulators.
13. Have received any investigational drug within 4 weeks before enrollment, or have participated in another clinical study at the same time.
14. Pregnant or lactating subjects, or those who are unwilling to contraception during the test.
15. Known uncontrolled diabetes, pulmonary fibrosis, interstitial lung disease, acute lung disease or liver failure.
16. Other serious organic diseases and mental disorders.
17. Have received any gene therapy products before.
18. According to the judgment of the researcher, those who are not suitable for the group, such as poor compliance.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
HRYZ-T101 TCR-T cell therapy	Fludarabine + Cyclophosphamide	Patients will undergo lymphocytapheresis, then treatment with TCR-T cell.
HRYZ-T101 TCR-T cell therapy	HRYZ-T101 TCR-T Cell	Patients will undergo lymphocytapheresis, then treatment with TCR-T cell.

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
Progression-Free Survival（PFS）	2 years	The length of time from enrollment until the time of progression of disease.
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.
Duration of TCR T cells in-vivo persistence	Up to 2 years	Blood samples were collected to measure persistence of infused HRYZ-T101.

Trial Locations

Locations (1)

Fudan University Shanghai Cancer Center; 🇨🇳 Shanghai, Shanghai, China