CRTE7A2-01 TCR-T Cell for HPV-16 Positive Advanced Cervical, Anal, or Head and Neck Cancers
Primary Purpose
Cervical Cancer, Anal Cancer, Head and Neck Cancers
Status
Recruiting
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
Fludarabine + Cyclophosphamide
Interleukin-2
CRTE7A2-01 TCR-T Cell
Sponsored by
About this trial
This is an interventional treatment trial for Cervical Cancer focused on measuring 3+3 dose escalation
Eligibility Criteria
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.
Sites / Locations
- The First Affiliated Hospital of Zhengzhou UniversityRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
CRTE7A2-01 TCR-T cell therapy
Arm Description
Patients will undergo lymphocytapheresis, then treatment with TCR-T cell (at escalating doses) + IL-2
Outcomes
Primary Outcome Measures
MTD
Maximum Tolerated Dose
DLT
Dose-limiting toxicity
RP2D
Recommended Phase II Dose
Incidence of treatment related AEs, AEs of special interest and serious adverse events (SAEs).
grade 1-5 (CTCAE)
Secondary Outcome Measures
Objective Response Rate(ORR)
Assessed by RECIST 1.1
Disease Control Rate(DCR)
Assessed by RECIST 1.1
Duration of Response(DOR)
Assessed by RECIST 1.1
Progression-Free Survival(PFS)
Assessed by RECIST 1.1
Full Information
NCT ID
NCT05122221
First Posted
November 5, 2021
Last Updated
June 22, 2022
Sponsor
Corregene Biotechnology Co., Ltd
1. Study Identification
Unique Protocol Identification Number
NCT05122221
Brief Title
CRTE7A2-01 TCR-T Cell for HPV-16 Positive Advanced Cervical, Anal, or Head and Neck Cancers
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
November 2021
Overall Recruitment Status
Recruiting
Study Start Date
July 17, 2022 (Anticipated)
Primary Completion Date
March 2023 (Anticipated)
Study Completion Date
December 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Corregene Biotechnology Co., Ltd
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No
5. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cervical Cancer, Anal Cancer, Head and Neck Cancers
Keywords
3+3 dose escalation
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
12 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
CRTE7A2-01 TCR-T cell therapy
Arm Type
Experimental
Arm Description
Patients will undergo lymphocytapheresis, then treatment with TCR-T cell (at escalating doses) + IL-2
Intervention Type
Drug
Intervention Name(s)
Fludarabine + Cyclophosphamide
Intervention Description
Fludarabine: 25mg/m²/day×3days Cyclophosphamide: 500mg/m²/day×3 days
Intervention Type
Drug
Intervention Name(s)
Interleukin-2
Intervention Description
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.
Intervention Type
Biological
Intervention Name(s)
CRTE7A2-01 TCR-T Cell
Intervention Description
On day 0, the TCR-T cells will be administered one time, each bag of cell intravenously within 20 minutes.
Primary Outcome Measure Information:
Title
MTD
Description
Maximum Tolerated Dose
Time Frame
28 days
Title
DLT
Description
Dose-limiting toxicity
Time Frame
28 days
Title
RP2D
Description
Recommended Phase II Dose
Time Frame
28 days
Title
Incidence of treatment related AEs, AEs of special interest and serious adverse events (SAEs).
Description
grade 1-5 (CTCAE)
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Objective Response Rate(ORR)
Description
Assessed by RECIST 1.1
Time Frame
2 years
Title
Disease Control Rate(DCR)
Description
Assessed by RECIST 1.1
Time Frame
2 years
Title
Duration of Response(DOR)
Description
Assessed by RECIST 1.1
Time Frame
2 years
Title
Progression-Free Survival(PFS)
Description
Assessed by RECIST 1.1
Time Frame
2 years
Other Pre-specified Outcome Measures:
Title
Peripheral blood TCR-T cell copy number
Time Frame
2 years
Title
Negative conversion rate among HPV-16 positive patients detected by tissue biopsy
Time Frame
2 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Sa Wang, Master
Phone
8610-86464526-840
Email
wangsa@corregene.com
Facility Information:
Facility Name
The First Affiliated Hospital of Zhengzhou University
City
Zhengzhou
State/Province
Henan
ZIP/Postal Code
450052
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yi Zhang, Doctor
Phone
0371-66295320
Email
yizhang@zzu.edu.cn
First Name & Middle Initial & Last Name & Degree
Yi Zhang, Doctor
12. IPD Sharing Statement
Plan to Share IPD
No
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CRTE7A2-01 TCR-T Cell for HPV-16 Positive Advanced Cervical, Anal, or Head and Neck Cancers
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