HPV-E6-Specific Anti-PD1 TCR-T Cells in the Treatment of HPV-Positive NHSCC or Cervical Cancer

Cervical Cancer Clinical Trial

Official title:

Two-Arm Open-Labeled Trial of HPV-E6-Specific TCR-T Cells With or Without Anti-PD1 Auto-secreted Element in the Treatment of HPV-Positive Head and Neck Carcinoma or Cervical Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03578406
• Other study ID #: XQDC20180520
• Status: Recruiting
• Phase: Phase 1
• Start date: September 1, 2018
• Est. completion date: August 30, 2021

Study information

• Verified date: April 2019
• Source: Xinqiao Hospital of Chongqing
• Contact: Qingzhu Jia
• Phone: +8615223334184
• Email: jiaqingzhu0801[@]outlook.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Human papillomavirus infections 16 (HPV16) is known to be a high-risk factor to induce cervical cancers. To date, HPV16-related cervical cancer is still a major concern in developing countries where vaccination is not prevalent. Concurrent therapies for cervical cancers have limited response rate and high chance of relapse. However, HPV16-induced cancers provided an ideal target for T cell-based immunotherapy due to the non-self origins. Engineered T cells bearing a TCR (TCR-T) that can specifically recognize the presented HPV antigen become a viable approach to treat this type of cancer. Though engineered T therapies have been well-recognized in hematological cancers, solid cancer treatment has been a major hurdle due to the immune-suppressive tumor microenvironment. One key mechanism of tumor-elicited suppression is the PDL1-PD1 interaction which induces T cell exhaustion. Therefore, TCR-T cells armed with a PD1 antagonist could further enhance the efficacy of TCR-T in solid cancers.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: August 30, 2021
• Est. primary completion date: August 30, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• Expected to live longer than 12 weeks

• PS 0-2

• Pathology confirmed as HPV16 positive malignant tumor, either metastatic or recurrent disease

• Creatinine <2.5mg/dl

• ALT/AST is lower than three times ULN.

• No contraindications of leukocyte collection

• Before entering the trial, women must adopt a reliable method of contraception until 30 days after infusion.

• Understand this trial and have signed an informed consent

Exclusion Criteria:

• Patients with symptomatic brain metastasis

• With other uncontrolled malignant tumors.

• Hepatitis B or Hepatitis C activity period, HIV infected patients

• Any other uncontrolled disease that interferes with the trial

• Patients with severe heart and cerebrovascular diseases such as coronary heart disease, angina pectoris, myocardial infarction, arrhythmia, cerebral thrombosis and cerebral hemorrhage

• Untreated hypertension or hypertensive patients

• A person with a history of mental illness that is difficult to control

• Researchers do not consider it appropriate to participate in this trial

• Patients who have been using immunosuppressive agents for a long time after organ transplants, except for recent or current inhaled corticosteroids

• Subjects who have been pregnant or nursing, or who plan for pregnancy within 2 months of treatment or after the end of treatment

• An illness affects a person who signs a written consent or complies with a study procedure, or who is unwilling or unable to comply with the research requirements

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Squamous Cell
• Cervical Cancer
• Head and Neck Squamous Cell Carcinoma
• Squamous Cell Carcinoma of Head and Neck
• Uterine Cervical Neoplasms

Intervention

Drug:
• HPV E6-specific TCR-T cells
Patients were infused with HPV E6-specific TCR-T cells

Locations

Country	Name	City	State
China	Qingzhu Jia	Chongqing	Chongqing

Sponsors (2)

Lead Sponsor	Collaborator
Xinqiao Hospital of Chongqing	TCRCure Biotech Co., Ltd

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To Determine the Maximum Tolerated Dose	Verify the MTD of TCR-T cells for HPV16 E6 antigen for treatment. Nine patients will be enrolled in this project, using a dose-climbing approach, with every three patients as a group. The first group of patients returned to 5x106/kg TCR-T cells, the second group returned to 1x107/kg TCR-T cells, and the third group returned to 5x107/kg TCR-T cells	8 weeks