crte7a2-01 tcr-t cell for hpv-16 positive advanced cervical, anal, or head and neck cancers

Conditions: Cervical Cancer; Anal Cancer; Head and Neck Cancers

Summary: a single center, open, single arm dose escalation phase i study to evaluate the safety, tolerability, and efficacy of crte7a2-01 tcr-t cell for hpv16 positive advanced cervical, anal, or head and neck cancers. the study will determine mtd of crte7a2-01 tcr-t cell injection, as well as investigate rp2d.


Eligibility criteria:
inclusion criteria: 1. age ≥18 years and ≤65 years. 2. histologically-confirmed cervical cancer, anal cancer, head and neck cancers with confirmed hpv16 infection and hla-a\*02:01 allele 3. failure on or intolerance to systemic therapy for unresectable advanced cancer. 4. ecog performance status of 0-1. 5. estimated life expectancy ≥ 3 months. 6. patients must have at least one measurable lesion defined by recist 1.1. 7. female patients of childbearing age must undergo a serum pregnancy test within 7 days prior to study treatment and the results must be negative, and are willing to use a very effective and reliable method of contraception from screening through 6 months after the last dose of study treatment. 8. the patient must be willing to sign the informed consent form and have a good anticipation of compliance with study procedure. exclusion criteria： 1. the proportion of t cell immune-related gene deletion mutations\>5%. 2. patient received any genetically modified t cell therapy. 3. patient who is being treated with t cell immunosuppressive agent （such as cyclophosphamide, fk506,tripterygium glycosides） or t cell immunoagonist. 4. patients received chemotherapy, targeted therapy, immunotherapy, or other investigational agents within 2 weeks and received radiotherapy within 4 weeks before apheresis. 5. patients with any organ dysfuntion as defined below: * leukocytes\<3.0 x 109/l * absolute neutrophil count \>1.5 x 109/l * hemoglobin\<90g/l * platelets \<100 x 1010/l * lymphocytes\<0.8 x 109/l * percentage of lymphocytes\<15% * creatinine\>1.5×uln or creatinine clearance \<50ml/min * total bilirubin\>3×uln; alt/ast\>3×uln (patients with liver metastasis,\>5×uln) * inr\>1.5×uln; aptt\>1.5×uln * spo2≤90% 6. patients with serious medical conditions, disorders, and / or comorbidities, including, but are not limited to: severe heart disease, cerebrovascular disease, epileptic seizures, uncontrolled diabetes (ctcae 5.0: fbg ≥ 2 grade), active infection, active digestive tract ulcer, gastrointestinal bleeding, intestinal obstruction, pulmonary fibrosis, renal failure, respiratory failure. 7. patient with a severe cardiovascular disease with 6 months before screening, including, but are not limited to, myocardial infarction, severe or unstable angina, coronary or peripheral artery bypass grafting, heart failure nyha grade ⅲ or ⅳ. 8. left ventricular ejection fractions (lvef) \<50%. 9. patient with a known active brain metastases. 10. patient with a known myelodysplastic syndrome (mds) or lymphoma. 11. patient with a known active autoimmune disease, including , but are not limited to, acquired or congenital immunodeficiency disease, allogeneic organ transplantation, autoimmune hepatitis, systemic lupus erythematosus, inflammatory bowel disease. 12. patient with a known active hepatitis b or hepatitis c. 13. patient with a history of human immunodeficiency virus (hiv) . 14. patient with a history of syphilis. 15. pregnant or lactating women. 16. patient with a known active mental and neurological diseases. 17. the principal investigator judged that it is not suitable to participate in this clinical study.

Keywords: 3+3 dose escalation