Clinical trial NCT05122221: 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
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Cervical Cancer
Anal Cancer
Head and Neck Cancers
Keywords: 3+3 dose escalation
Lead sponsor: Corregene Biotechnology Co., Ltd
Sponsor class: INDUSTRY
First posted: 2021-11-16
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: MTD
timeFrame: 28 days
measure: DLT
timeFrame: 28 days
measure: RP2D
timeFrame: 28 days
measure: Incidence of treatment related AEs, AEs of special interest and serious adverse events (SAEs).
timeFrame: 2 years
Secondary outcomes:
measure: Objective Response Rate（ORR）
timeFrame: 2 years
measure: Disease Control Rate（DCR）
timeFrame: 2 years
measure: Duration of Response（DOR）
timeFrame: 2 years
measure: Progression-Free Survival（PFS）
timeFrame: 2 years
Other outcomes:
measure: Peripheral blood TCR-T cell copy number
timeFrame: 2 years
measure: Negative conversion rate among HPV-16 positive patients detected by tissue biopsy
timeFrame: 2 years
Locations:
city: Zhengzhou
country: China
facility: The First Affiliated Hospital of Zhengzhou University
state: Henan
Study officials:
References: