NCT05357027

HPV16 E6 TCR T Cells for Cervical Carcinoma

A Phase I/II Clinical Trail of TC-E202 Targeting HPV16 E6 for Relapsed/Refractory to Standard Treatment or Metastatic Cervical Carcinoma

• Status: Terminated
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 5 (actual)
• Sponsor: TCRCure Biopharma Ltd. · Industry
• Sex: Female
• Age: 18 Years – 70 Years
• Healthy volunteers: Not accepted

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 an 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.

Detailed description

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 an HPV protein called E6. E6 is the main factors of HPV 16 carcinogenesis. T cells genetically engineered with a TCR targeting HPV-16 E6 (E6 TCR) display specific reactivity against HLA-A2+, HPV-16+ target cells. T cell receptor (TCR) gene engineered T cells infusion can induce objective tumor responses in certain malignancies including HPV-16+ cancer. Objective: Phase I: Determine the safety and tolerability of TC-E202 inHPV16 positive patients with relapsed/refractory to standard treatment or metastatic cervical carcinoma and determine the Recommended Phase II Dose (RPIID). Primary endpoints: safety and tolerability. The evaluation of safety and tolerability will be based on the following endpoints: 1) Whether DLT occurs or MTD is achieved; 2) The incidence of various adverse events and serious adverse events and their relationship with TCR-T, IL-2, lymphodepletion chemotherapy and leukapheresis. Secondary endpoints: efficacy. Objective response rate (ORR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS) were assessed based on RECIST 1.1 and iRECIST. Eligibility: Adults aging 18-70 with relapsed/refractory to standard treatment or metastatic cervical carcinoma. Eligible patients were HLA-A\*02 and had metastatic HPV16-positive cervical cancer. Patients had received or declined previous systemic therapy, with more than 4 weeks elapsed since previous systemic treatment. Patients had an Eastern Cooperative Oncology Group performance score of 0 or 1 and adequate hematologic, hepatic, and renal function. Design: This is a Phase I/II clinical trial to evaluate the efficacy and safety of TC-E202. Dose escalation will proceed according to 3+3 procedure. All patients will receive a lymphocyte-depleting preparative regimen of cyclophosphamide and fludarabine followed by an infusion of E6 TCR (TC-E202) cells. Cell infusion will be followed by IL-2 administration. All patents will be evaluated based on ORR according to RECIST v1.1\&iRECIST. Phase I clinical trials establish a Drug Safety Review Committee (SRC), and the SRC will hold regular and irregular meetings to evaluate the safety data of the subjects, the clinical pharmacology, along with associated clinical efficacy, to decide escalating dose and RPIID. In addition, the SRC will decide whether to explore higher or lower doses than planned doses based on specific data.

Conditions

• Cervical Carcinoma

Interventions

Type	Name	Description
BIOLOGICAL	TC-E202 cells	T cells genetically engineered with a TCR targeting HPV16 E6 (E6 TCR) that display specific reactivity against HLA-A2+, HPV-16+ target cells
DRUG	IL-2	Following cell infusion, the patient receives high-dose bolus IL-2, which is dosed to individual patient tolerance. IL-2 improves the survival of TC-E202 cells after infusion.
DRUG	Fludarabine	Part of the non-myeloablative lymphocyte-depleting preparative regimen.
DRUG	Cyclophosphamide Capsules	Part of the non-myeloablative lymphocyte-depleting preparative regimen.

Timeline

• Start date: 2022-08-10
• Primary completion: 2026-01-15
• Completion: 2026-01-15
• First posted: 2022-05-02
• Last updated: 2026-01-21

Locations

1 site across 1 country: China