HRYZ-T101 Injection for HPV18 Positive Solid Tumor

Phase 1

Recruiting

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

• Registration Number: NCT05952947
• Lead Sponsor: HRYZ Biotech Co.

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.

Detailed Description

Not available

Study Timeline

• Status Verified: 2023-06
• Study First Submitted: 2023-07-05
• Study First Submitted QC: 2023-07-17
• Study First Posted: 2023-07-19
• Study Start: 2023-11-01
• Last Update Submitted: 2024-01-31
• Last Update Posted: 2024-02-02
• Primary Completion: 2027-12
• Study Completion: 2028-02

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 32

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:

  10. Leukocytes≥3.0 x 10^9/L;

  11. blood platelets ≥75 x 10^9/L;

  12. hemoglobin≥85g/L;

  13. Absolute lymphocyte count≥0.8 x 10^9/L

  14. Serum albumin ≥ 30g/L;

  15. total bilirubin≤1.5×ULN; ALT/AST≤3×ULN or ≤5×ULN for liver metastases;

  16. Creatinine clearance ≥50mL/min; or serum creatinine ≤1.5×ULN;

  17. INR≤1.5×ULN; APTT≤1.5×ULN;

  18. LVEF≥50%;

  19. 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

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

Primary Outcome Measures

Name	Time	Method
DLT	28 days	Dose-limiting toxicity
Adverse events and serious adverse events	2 years	Incidence of adverse events and serious adverse events

Secondary Outcome Measures

Name	Time	Method
Objective Response Rate（ORR）	2 years	The percentage of subjects with PR or CR assessed by RECIST 1.1.
Progression-Free Survival（PFS）	2 years	The length of time from enrollment until the time of progression of disease.
Duration of response (DoR)	2 years	Subjects who show a confirmed CR or PR as 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.
Disease Control Rate (DCR)	2 years	The percentage of subjects with a confirmed CR, PR, or stable disease (SD) 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.
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.

Trial Locations

Locations (1)

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