hryz-t101 injection for hpv18 positive solid tumor

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

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.


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.