CRTE7A2-01 TCR-T Cell for HPV-16 Positive Advanced Cervical, Anal, or Head and Neck Cancers
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: CRTE7A2-01 TCR-T cell therapy Patients will undergo lymphocytapheresis, then treatment with TCR-T cell (at escalating doses) + IL-2 |
Drug: Fludarabine + Cyclophosphamide
Fludarabine: 25mg/m²/day×3days Cyclophosphamide: 500mg/m²/day×3 days
Drug: Interleukin-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.
Biological: CRTE7A2-01 TCR-T Cell
On day 0, the TCR-T cells will be administered one time, each bag of cell intravenously within 20 minutes.
|
Outcome Measures
Primary Outcome Measures
- MTD [28 days]
Maximum Tolerated Dose
- DLT [28 days]
Dose-limiting toxicity
- 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)
Secondary Outcome Measures
- Objective Response Rate（ORR） [2 years]
Assessed by RECIST 1.1
- Disease Control Rate（DCR） [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
Other Outcome Measures
- Peripheral blood TCR-T cell copy number [2 years]
- Negative conversion rate among HPV-16 positive patients detected by tissue biopsy [2 years]
Eligibility Criteria
Criteria
Inclusion Criteria:
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Age ≥18 years and ≤65 years.
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Histologically-confirmed cervical cancer, anal cancer, head and neck cancers with confirmed HPV16 infection and HLA-A*02:01 allele
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Failure on or intolerance to systemic therapy for unresectable advanced cancer.
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ECOG performance status of 0-1.
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Estimated life expectancy ≥ 3 months.
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Patients must have at least one measurable lesion defined by RECIST 1.1.
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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.
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The patient must be willing to sign the informed consent form and have a good anticipation of compliance with study procedure.
Exclusion Criteria：
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The proportion of T cell immune-related gene deletion mutations>5%.
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Patient received any genetically modified T cell therapy.
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Patient who is being treated with T cell immunosuppressive agent （such as cyclophosphamide, FK506,tripterygium glycosides） or T cell immunoagonist.
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Patients received chemotherapy, targeted therapy, immunotherapy, or other investigational agents within 2 weeks and received radiotherapy within 4 weeks before apheresis.
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Patients with any organ dysfuntion as defined below:
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leukocytes<3.0 x 109/L
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absolute neutrophil count >1.5 x 109/L
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hemoglobin<90g/L
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platelets <100 x 1010/L
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lymphocytes<0.8 x 109/L
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percentage of lymphocytes<15%
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creatinine>1.5×ULN or creatinine clearance <50mL/min
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total bilirubin>3×ULN; ALT/AST>3×ULN (patients with liver metastasis,>5×ULN)
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INR>1.5×ULN; APTT>1.5×ULN
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SpO2≤90%
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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.
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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.
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Left Ventricular Ejection Fractions (LVEF) <50%.
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Patient with a known active brain metastases.
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Patient with a known myelodysplastic syndrome (MDS) or lymphoma.
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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.
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Patient with a known active Hepatitis B or Hepatitis C.
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Patient with a history of Human Immunodeficiency Virus (HIV) .
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Patient with a history of syphilis.
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Pregnant or lactating women.
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Patient with a known active mental and neurological diseases.
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The principal investigator judged that it is not suitable to participate in this clinical study.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | The First Affiliated Hospital of Zhengzhou University | Zhengzhou | Henan | China | 450052 |
Sponsors and Collaborators
- Corregene Biotechnology Co., Ltd
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CRTE7A2-2107C