Clinical trial NCT06358053: CRTE7A2-01 TCR-T Cells for HPV-16 Positive Advanced Cancers
Official title: A Phase I Study to Evaluate the Safety, Tolerance and Efficacy of CRTE7A2-01 TCR-T Cells in HLA-A*02:01+ Subjects With HPV16 Positive Advanced Cervical, Anal, or Head and Neck Cancers and Other Solid Tumors
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
Conditions: Cervical Cancer
Anal Cancer
Head and Neck Cancers
Other Solid Tumors
Keywords: HPV
E7
immunotherapy
T cell
Adoptive cell therapy
T cell receptor
TCR
Lead sponsor: Corregene Biotechnology Co., Ltd
Sponsor class: INDUSTRY
First posted: 2024-04-10
Enrollment: 24
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 and dose expansion phase I study to evaluate the safety, tolerability, and efficacy of CRTE7A2-01 TCR-T cells in HLA-A\*02:01+ Subjects HPV16 positive advanced cervical, anal, or head and neck cancers. The study will determine RP2D of CRTE7A2-01 TCR-T cell injection.


Eligibility criteria: Inclusion Criteria:

1. Age \>18 years and 65 years. 2. Patients with advanced solid tumors (such as cervical cancer, head and neck tumors, anal cancer, and other malignancies) who have failed standard treatment confirmed by histology and/or cytology, or who are intolerant to such treatment, and for whom there is no effective therapy available after standard treatment failure are considered as end-stage patients. Specifically for:

1. Cervical cancer: a) Patients who have previously failed at least second-line systemic therapy (including at least one platinum-based regimen or anti-angiogenic therapy) and have shown disease progression or intolerance confirmed by pathological or radiological examination during or after the most recent treatment course, and are not amenable to treatment with surgery or radiotherapy, with no standard treatment options currently available for recurrent or metastatic cervical cancer.
2. Nasopharyngeal cancer: a) Patients who have previously failed at least third-line systemic therapy or are intolerant, not amenable to treatment with surgery or radiotherapy, with no standard treatment options currently available for recurrent or metastatic nasopharyngeal cancer; b) EB virus negative.
3. Head and neck squamous cell carcinoma: a) Patients who have previously failed at least second-line systemic therapy or are intolerant, with no standard treatment options currently available for recurrent or metastatic head and neck squamous cell carcinoma (non-nasal).

3. Confirmation of HPV16 positive and HLA-A\*02:01 allele. 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. Patient received any genetically modified T cell therapy.
2. Patient is being treated with T cell immunosuppressive agent （such as cyclophosphamide, FK506,tripterygium glycosides） or T cell immunoagonist.
3. Patients received chemotherapy, targeted therapy, immunotherapy, or other investigational agents within 2 weeks and received radiotherapy within 4 weeks before apheresis.
4. Patients have any organ system function impairment 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\<0.5 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. Patinets has 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 has 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 has a known active brain metastases. 10. Patient has a known myelodysplastic syndrome (MDS) or lymphoma. 11. Patient has 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 has a known active Hepatitis B or Hepatitis C. 13. Patient has a history of Human Immunodeficiency Virus (HIV) . 14. Patient has a history of syphilis. 15. Pregnant or lactating women. 16. Patient has 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: DLT
timeFrame: 28 days
measure: RP2D
timeFrame: 2 years
measure: cevents (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
measure: Overall Survival(OS)
timeFrame: 2 years
Other outcomes:
measure: Peripheral blood TCR-T cell copy number
timeFrame: 2 years
Locations:
Study officials:
affiliation: Peking Union Medical College Hospital
name: Yang Xiang, Doctor
role: PRINCIPAL_INVESTIGATOR
References: