HRYZ-T101 Injection for HPV18 Positive Solid Tumor

NCT ID: NCT05952947

Last Updated: 2024-02-02

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 32 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-11-01
• Study Completion Date: 2028-02-29

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.

Conditions

Cervical Cancer; Head and Neck Squamous Cell Carcinoma; Carcinoma of Vagina; Carcinoma of Penis; Anal Cancer; Carcinoma of Vulva

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

HRYZ-T101 Injection

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

Group Type: EXPERIMENTAL

HRYZ-T101 Injection

Intervention Type: BIOLOGICAL

On day 1, the TCR-T cells will be administered intravenously.

Fludarabine + Cyclophosphamide

Intervention Type: DRUG

Fludarabine: 25mg/m²/day×3days; Cyclophosphamide: 250mg/m²/day×3 days

Interventions

HRYZ-T101 Injection

On day 1, the TCR-T cells will be administered intravenously.

Intervention Type: BIOLOGICAL

Fludarabine + Cyclophosphamide

Fludarabine: 25mg/m²/day×3days; Cyclophosphamide: 250mg/m²/day×3 days

Intervention Type: DRUG

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:

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

HRYZ Biotech Co.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Xiaohua Wu, Doctor

Role: PRINCIPAL_INVESTIGATOR

Fudan University

Jian Zhang, Doctor

Role: PRINCIPAL_INVESTIGATOR

Fudan University

Locations

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

Xuemin Rao

Role: CONTACT

raoxuemin@shhryz.com

021-61049928

Facility Contacts

Xuemin Rao

Role: primary

raoxuemin@shhryz.com

Other Identifiers

H-T01-C2001

Identifier Type: -

Identifier Source: org_study_id