CRTE7A2-01 TCR-T Cell for HPV-16 Positive Advanced Cervical, Anal, or Head and Neck Cancers

Study Overview
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Brief Summary
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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.

Official Title
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A Phase I Study to Evaluate the Safety, Tolerance and Efficacy of CRTE7A2-01 TCR-T Cell for HPV16 Positive Advanced Cervical, Anal, or Head and Neck Cancers

Conditions
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Cervical Cancer, Anal Cancer, Head and Neck Cancers

Intervention / Treatment
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* Drug: Fludarabine + Cyclophosphamide
* Drug: Interleukin-2
* Biological: CRTE7A2-01 TCR-T Cell


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 years and ≤65 years. Histologically-confirmed cervical cancer, anal cancer, head and neck cancers with confirmed HPV16 infection and HLA-A*02:01 allele Failure on or intolerance to systemic therapy for unresectable advanced cancer. ECOG performance status of 0-1. Estimated life expectancy ≥ 3 months. Patients must have at least one measurable lesion defined by RECIST 1.1. 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. The patient must be willing to sign the informed consent form and have a good anticipation of compliance with study procedure. Exclusion Criteria： The proportion of T cell immune-related gene deletion mutations>5%. Patient received any genetically modified T cell therapy. Patient who is being treated with T cell immunosuppressive agent （such as cyclophosphamide, FK506,tripterygium glycosides） or T cell immunoagonist. Patients received chemotherapy, targeted therapy, immunotherapy, or other investigational agents within 2 weeks and received radiotherapy within 4 weeks before apheresis. 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% 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. 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. Left Ventricular Ejection Fractions (LVEF) <50%. Patient with a known active brain metastases. Patient with a known myelodysplastic syndrome (MDS) or lymphoma. 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. Patient with a known active Hepatitis B or Hepatitis C. Patient with a history of Human Immunodeficiency Virus (HIV) . Patient with a history of syphilis. Pregnant or lactating women. Patient with a known active mental and neurological diseases. The principal investigator judged that it is not suitable to participate in this clinical study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CRTE7A2-01 TCR-T cell therapy<br>Patients will undergo lymphocytapheresis, then treatment with TCR-T cell (at escalating doses) + IL-2 | Drug: Fludarabine + Cyclophosphamide<br>* Fludarabine: 25mg/m²/day×3days Cyclophosphamide: 500mg/m²/day×3 days<br>Drug: Interleukin-2<br>* 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.<br>Biological: CRTE7A2-01 TCR-T Cell<br>* On day 0, the TCR-T cells will be administered one time, each bag of cell intravenously within 20 minutes.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MTD | Maximum Tolerated Dose | 28 days | 
| DLT | Dose-limiting toxicity | 28 days | 
| RP2D | Recommended Phase II Dose | 28 days | 
| Incidence of treatment related AEs, AEs of special interest and serious adverse events (SAEs). | grade 1-5 (CTCAE) | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate（ORR） | Assessed by RECIST 1.1 | 2 years | 
| Disease Control Rate（DCR） | Assessed by RECIST 1.1 | 2 years | 
| Duration of Response（DOR） | Assessed by RECIST 1.1 | 2 years | 
| Progression-Free Survival（PFS） | Assessed by RECIST 1.1 | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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3+3 dose escalation