HPV16 E6 TCR T Cells for Cervical Carcinoma

Launched by TCRCURE BIOPHARMA LTD. · Apr 26, 2022

Keywords

ClinConnect Summary

This clinical trial is studying a new treatment for cervical cancer that is linked to the human papillomavirus (HPV), specifically a protein called E6. The treatment involves taking a patient's own blood, isolating specific immune cells called T cells, and then modifying them in a lab to target cancer cells that express the E6 protein. These specially engineered T cells, known as E6 TCR-T cells, are then given back to the patient to help their body fight the cancer.

To be eligible for this trial, participants must be women aged 18 to 70 who have cervical cancer that has returned or is not responding to standard treatments. They also need to have a specific type of HPV and meet certain health criteria. Participants can expect to undergo some tests to check their overall health, and the process will involve a procedure to collect their blood and then receive the engineered cells. Throughout the trial, they will be closely monitored for safety and how well the treatment works. It's important to know that this is an early-stage trial, meaning researchers are primarily focused on understanding if the treatment is safe and effective before it becomes widely available.

Gender

FEMALE

Eligibility 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.