Anal Cancer, Cervical Cancer, Head and Neck Cancers
Conditions
Keywords
3+3 dose escalation
Brief 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.
Interventions
Fludarabine: 25mg/m²/day×3days Cyclophosphamide: 500mg/m²/day×3 days
DRUGInterleukin-2
Interleukin-2 20,000,000 IU/time infused within 15 minutes approximately every 8 hours (according to the subject's tolerance, the interval between medications can be extended to 24 hours) for a maximum usage time up to 14 days.
BIOLOGICALCRTE7A2-01 TCR-T Cell
On day 0, the TCR-T cells will be administered one time, each bag of cell intravenously within 20 minutes.
Sponsors
Corregene Biotechnology Co., Ltd
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| RP2D | 28 days | Recommended Phase II Dose |
| Incidence of treatment related AEs, AEs of special interest and serious adverse events (SAEs). | 2 years | grade 1-5 (CTCAE) |
| MTD | 28 days | Maximum Tolerated Dose |
| DLT | 28 days | Dose-limiting toxicity |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate（ORR） | 2 years | Assessed by RECIST 1.1 |
| Duration of Response（DOR） | 2 years | Assessed by RECIST 1.1 |
| Progression-Free Survival（PFS） | 2 years | Assessed by RECIST 1.1 |
| Disease Control Rate（DCR） | 2 years | Assessed by RECIST 1.1 |
Other
| Measure | Time frame |
|---|---|
| Negative conversion rate among HPV-16 positive patients detected by tissue biopsy | 2 years |
| Peripheral blood TCR-T cell copy number | 2 years |
Countries
China
Contacts
Primary ContactSa Wang, Master
Outcome results
None listed