Using engineered T cells to treat cervical cancer caused by HPV16
A Phase I/II Clinical Trail of TC-E202 Targeting HPV16 E6 for Relapsed/Refractory to Standard Treatment or Metastatic Cervical Carcinoma
This study is testing a new treatment using specially modified T cells to see if it can help people with cervical cancer caused by HPV16 feel better and live longer.
Quick facts
| Phase | Phase1; Phase2 |
|---|---|
| Study type | Interventional |
| Enrollment | 18 (estimated) |
| Ages | 18 Years to 70 Years |
| Sex | Female |
| Sponsor | TCRCure Biopharma Ltd. Industry-sponsored |
| Drugs / interventions | CAR-T, chemotherapy, cyclophosphamide, fludarabine |
| Locations | 1 site (Chongqing, Chongqing) |
| Trial ID | NCT05357027 on ClinicalTrials.gov |
What this trial studies
This clinical trial evaluates the safety and efficacy of T cell receptor (TCR) engineered T cells targeting the HPV16 E6 protein in patients with relapsed or metastatic cervical carcinoma. Patients aged 18-70 who have previously undergone standard treatments will undergo leukapheresis to collect T cells, which will then be genetically modified to enhance their ability to attack HPV-infected cancer cells. The trial will assess both the safety of the treatment and its effectiveness in shrinking tumors and improving patient survival.
Who should consider this trial
Good fit: Ideal candidates are adults aged 18-70 with HPV16 positive, relapsed or metastatic cervical carcinoma who have failed at least second-line standard treatment.
Not a fit: Patients with cervical carcinoma that is not HPV16 positive or those who have not received prior treatments may not benefit from this study.
Why it matters
Potential benefit: If successful, this treatment could provide a novel and effective option for patients with advanced cervical cancer that is resistant to standard therapies.
How similar studies have performed: Other studies using TCR T cell therapy for HPV-related cancers have shown promising results, indicating potential for success in this approach.
Eligibility criteria
Show full inclusion / exclusion 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.
Where this trial is running
Chongqing, Chongqing
- Xiaochun Cheng — Chongqing, Chongqing, China (Recruiting)
Study contacts
- Study coordinator: XiaoHua Wu, doctor
- Email: Wu.XH@Fudan.edu.cm
- Phone: +86-2164175590
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.