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.

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.