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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| CRTE7A2-01 TCR-T cell therapy | Experimental | Patients will undergo lymphocytapheresis, then treatment with TCR-T cell (at escalating doses) + IL-2 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Fludarabine + Cyclophosphamide | Drug | Fludarabine: 25mg/m²/day×3days Cyclophosphamide: 500mg/m²/day×3 days |
|
| 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 |
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Peripheral blood TCR-T cell copy number | 2 years | |
| Negative conversion rate among HPV-16 positive patients detected by tissue biopsy | 2 years |
Inclusion Criteria:
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:
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.
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Sa Wang, Master | Contact | 8610-86464526-840 | wangsa@corregene.com |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The First Affiliated Hospital of Zhengzhou University | Recruiting | Zhengzhou | Henan | 450052 | China |
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| ID | Term |
|---|---|
| D002583 | Uterine Cervical Neoplasms |
| D001005 | Anus Neoplasms |
| D006258 | Head and Neck Neoplasms |
| ID | Term |
|---|---|
| D014594 | Uterine Neoplasms |
| D005833 | Genital Neoplasms, Female |
| D014565 | Urogenital Neoplasms |
| D009371 | Neoplasms by Site |
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| ID | Term |
|---|---|
| C024352 | fludarabine |
| D003520 | Cyclophosphamide |
| D007376 | Interleukin-2 |
| ID | Term |
|---|---|
| D010752 | Phosphoramide Mustards |
| D009588 | Nitrogen Mustard Compounds |
| D009150 | Mustard Compounds |
| D006846 | Hydrocarbons, Halogenated |
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| Interleukin-2 | Drug | 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. |
|
| CRTE7A2-01 TCR-T Cell | Biological | On day 0, the TCR-T cells will be administered one time, each bag of cell intravenously within 20 minutes. |
|
| Duration of Response(DOR) | Assessed by RECIST 1.1 | 2 years |
| Progression-Free Survival(PFS) | Assessed by RECIST 1.1 | 2 years |
| D009369 |
| Neoplasms |
| D002577 | Uterine Cervical Diseases |
| D014591 | Uterine Diseases |
| D005831 | Genital Diseases, Female |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D000091662 | Genital Diseases |
| D012004 | Rectal Neoplasms |
| D015179 | Colorectal Neoplasms |
| D007414 | Intestinal Neoplasms |
| D005770 | Gastrointestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
| D004066 | Digestive System Diseases |
| D005767 | Gastrointestinal Diseases |
| D007410 | Intestinal Diseases |
| D001004 | Anus Diseases |
| D012002 | Rectal Diseases |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D063088 | Phosphoramides |
| D009943 | Organophosphorus Compounds |
| D007378 | Interleukins |
| D016207 | Cytokines |
| D036341 | Intercellular Signaling Peptides and Proteins |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D008222 | Lymphokines |
| D011506 | Proteins |
| D001685 | Biological Factors |