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

• ClinicalTrials.gov Identifier: NCT03578406
• Recruitment Status: Recruiting
• First Posted: July 6, 2018
• Last Update Posted: May 1, 2019
• Sponsor: Xinqiao Hospital of Chongqing
• Collaborator: TCRCure Biotech Co., Ltd
• Information provided by (Responsible Party): Qingzhu Jia, M.D., Xinqiao Hospital of Chongqing

Study Description

Brief 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.

Condition or disease	Intervention/treatment	Phase
Cervical Cancer; Head and Neck Squamous Cell Carcinoma	Drug: HPV E6-specific TCR-T cells	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 20 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: September 1, 2018
• Estimated Primary Completion Date: August 30, 2020
• Estimated Study Completion Date: August 30, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: HPV TCR-T; HPV E6-specific TCR-T cell	Drug: HPV E6-specific TCR-T cells; Patients were infused with HPV E6-specific TCR-T cells
Experimental: HPV TCR-T with anti-PD1; HPV E6-specific TCR-T cell with anti-PD1 auto-secreted element	Drug: HPV E6-specific TCR-T cells; Patients were infused with HPV E6-specific TCR-T cells

Outcome Measures

Primary Outcome Measures :

1. To Determine the Maximum Tolerated Dose [ Time Frame: 8 weeks ]
   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

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 70 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Contacts

Contact: Qingzhu Jia; +8615223334184 ext +8615223334184; jiaqingzhu0801@outlook.com

Locations

China, Chongqing

Qingzhu Jia; Recruiting

Chongqing, Chongqing, China, 400037

Contact: Qingzhu Jia +8615223334184 ext +8615223334184 jiaqingzhu0801@outlook.com

Sponsors and Collaborators

Xinqiao Hospital of Chongqing

TCRCure Biotech Co., Ltd

Investigators

• Principal Investigator: Bo Zhu; Oncology of Department, Xinqiao Hospital

More Information

• Responsible Party: Qingzhu Jia, M.D., Secretary of Research, Xinqiao Hospital of Chongqing
• ClinicalTrials.gov Identifier: NCT03578406
• Other Study ID Numbers: XQDC20180520
• First Posted: July 6, 2018
• Last Update Posted: May 1, 2019
• Last Verified: April 2019

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Carcinoma; Uterine Cervical Neoplasms; Squamous Cell Carcinoma of Head and Neck; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Carcinoma, Squamous Cell; Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Uterine Cervical Diseases; Uterine Diseases; Head and Neck Neoplasms