HRYZ-T101 Injection for HPV18 Positive Solid Tumor

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

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.

Study Overview

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

• Study Type: Interventional
• Enrollment (Estimated): 32
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Xuemin Rao; Phone Number: 021-61049928; Email: raoxuemin@shhryz.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China
      • Recruiting
      • Fudan University Shanghai Cancer Center
      • Principal Investigator: Xiaohua Wu, Doctor
      • Principal Investigator: Jian Zhang, Doctor
      • Contact: Xuemin Rao; Email: raoxuemin@shhryz.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HRYZ-T101 Injection; Patients will undergo lymphocytapheresis, then treatment with HRYZ-T101 TCR-T cells.	Drug: Fludarabine + Cyclophosphamide; Fludarabine: 25mg/m²/day×3days; Cyclophosphamide: 250mg/m²/day×3 days; Biological: HRYZ-T101 Injection; On day 1, the TCR-T cells will be administered intravenously.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
DLT	Dose-limiting toxicity	28 days
Adverse events and serious adverse events	Incidence of adverse events and serious adverse events	2 years

Secondary Outcome Measures

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects with positive anti-drug antibodies (ADA)	Serum samples will be collected to analyze for the presence of ADAs using validated immunoassays.	2 years
Number of subjects with replication competent lentivirus (RCL)	RCL exposure will be assessed by polymerase chain reaction (PCR) based assay.	2 years
T cell subgroup in peripheral blood	Collect blood samples and analyze for T cell subgroup by flow cytometry at specified intervals before and after treatment with HRYZ-T101.	2 years

Collaborators and Investigators

• Sponsor: HRYZ Biotech Co.
• Investigators: Principal Investigator: Jian Zhang, Doctor, Fudan University; Principal Investigator: Xiaohua Wu, Doctor, Fudan University

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2023
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): February 1, 2028

Study Registration Dates

• First Submitted: July 5, 2023
• First Submitted That Met QC Criteria: July 17, 2023
• First Posted (Actual): July 19, 2023

Study Record Updates

• Last Update Posted (Estimated): February 2, 2024
• Last Update Submitted That Met QC Criteria: January 31, 2024
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Genital Neoplasms, Female; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Head and Neck Neoplasms; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Vaginal Diseases; Vulvar Diseases; Carcinoma, Squamous Cell; Rectal Neoplasms; Anus Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Carcinoma; Squamous Cell Carcinoma of Head and Neck; Vulvar Neoplasms; Anus Neoplasms; Vaginal Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Cyclophosphamide; Fludarabine
• Other Study ID Numbers: H-T01-C2001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No