HPV16 E6 TCR T Cells for Cervical Carcinoma

• Status: Not yet recruiting
• Trial end date: 2024-08-31
• Target enrollment: 0
• Participant gender: Female

Summary

Background:

Cervical cancer is the most common gynecologic malignant tumor .The occurrence and progression of cervical carcinoma is firmly relevant to HPV (Human papilloma virus) infection. Cancer cells infected by HPV expressing a HPV protein called E6. E6 is the main factors of HPV 16 carcinogenesis. In TCR-T therapy, researchers take the blood of a certain patient, select T cells and insert genes into the cell that expressing a kind of protein that targeting HPV E6. The genetically engineered cells are called E6 TCR-T cells. The engineered cells are re-infused in the patients with cervical carcinoma.

Objective:

To evaluate the safety and efficacy of TCR-T cells in the treatment of cervical carcinoma.

Eligibility:

Adults aging 18-70 with relapsed/refractory to standard treatment or metastatic cervical carcinoma.

Design:

Patients will have many screening tests, including imaging procedures, heart and lung tests, and lab tests.

Patients will have leukapheresis. Blood will be removed through a needle in the arm. A machine separates the white blood cells. The rest of the blood is returned through a needle in the other arm.

Engineered T cells will be re-infused into the patients will stay in hospital and be evaluated.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: TCRCure Biopharma Ltd.
• Collaborator: Fudan University
• Treatments: Cyclophosphamide; Fludarabine

Criteria

Inclusion Criteria:

1. Be able to understand and sign the Informed of Consent Document. Be willing to follow the procedure and protocol of the clinical trial.

2. Age ≥ 18 years and ≤ 70 years.

3. Expected survival time > 3 months.

4. ECOG score 0-1.

5. Recurrent or metastatic cervical carcinoma based on TNM & FIGO staged histopathological investigation.

6. Received at least second-line standard treatment and diagnosed as PD through image assessment. (previously received radio-therapy, chemo-therapy, targeted-therapy or immune-therapy, wash-out period > 14 or 5 half life)

7. Be able provide fresh or preserved tissue specimen. (fresh specimen first, paraffine specimen or at least 12 tumor section, tumor tissue >20%)

8. At least 1 measurable lesion (according to RECIST1.1 standard）.

9. HPV16 positive.

10. HLA-A2 positive.

11. Hematology should at least meet the following criteria:

Absolute neutrophil count (ANC) ≥ 1.5× 109/L (±20%)； Platelet (PLT） ≥ 75× 109/L (±20%）； Hemoglobin (HGB) ≥ 90 g/L (±20%).

12. Blood biochemistry should at least meet the following criteria:

Serum creatinine (Cr) ≤ 1.5 times of upper limit of normal (ULN) or creatine clearance ≥ 60 ml/min; Serum Alanine aminotransferase (ALT) or/and Aspartate aminotransferase (AST) ≤ 2.5 times of upper limit of normal; Total bilirubin (TBIL) ≤ 15 times of upper limit of normal.

13. Blood coagulation function is normal: Prothrombin time (PT) ≤ 1.5 ULN, International Normalized Ratio (INR) ≤ 1.5 ULN, or Activated Partial Thromboplastin Time (APTT) ≤ 1.5 ULN.

14. Women of childbearing potential should be ascetic or take contraception since the signing of ICF to 24 weeks or later after the last administration of drug.

15. Recovered from toxic effect of previous treatment (CTCAE ≤ 1), or related AE(s) is not defined as safety issue.

16. Catheter insertion is feasible and No White Blood Cells collection contraindications.

Exclusion Criteria:

1. Under pregnancy or lactation, or positive based on blood pregnancy test.

2. Severe allergic to related ingredients in the clinical trial.

3. Received any other investigational treatment within 4 weeks before the first administration or enrolled in another clinical trial the same time (exception: the other treatment is observational and non-investigational or the patient is under follow-up period)

4. Primary central nerve system (CNS) cancer, or subjects with CNS metastasis after localized treatment (except patients without CNS metastasis, clinically stable and neither steroid treatment nor treatment for CNS metastasis).

5. Patients with active autoimmune disease or require systemic steroid treatment. (except patients with cutaneous condition but without systemic treatment, or subjects with asthma in childhood but without intervention after grown-up, or subjects with hypothyroidism mediated by autoimmune dysfunction and receiving thyroxine as replaced treatment)

6. Immunodeficiency including HIV positive, harvested or natural immunodeficiency.

7. Patients with ≥ grade 3 thromboembolic events within 2 years or under thrombolysis treatment.

8. Patients with hereditary or acquired hemorrhagic disease

9. Patients with cardiovascular disease or symptoms:

congestive heart failure (NYHA > 2); history of unstable angina pectoris; miocardial infarction within 48 weeks; clinically significant malignant arrhythmia (except atrial fibrillation and paroxysmal supraventricular tachycardia); Clinically significant prolonged QTcF (Male QTcF > 450 msec, Female QTcF > 470 msec); Uncontrolled hypertension.

10. Patients under active infection (except subjects with fever caused by tumor)

11. Patients with active tuberculosis, or history of active tuberculosis within 1 year before enrollment, or history of active tuberculosis over a year before enrollment but without standard treatment.

12. Patient with Active Hepatitis B or Active Hepatitis C.

13. Treponema pallidum antibody positive.

14. Received major surgery or under severe injury within 4 weeks before enrollment.

15. History of drug abuse, alcohol or drug addiction.

16. Received cell therapy before enrollment，such as TCR-T，CAR-T and TIL .

17. Allergic to IL-2.

18. Received treatment related chemo-therapy within 14 days of TC-E202 infusion (except lymphodepletion) .

19. Patient not suitable for the clinical trial according to investigators.