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

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

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.

Study Overview

• Status: Unknown
• Conditions: Cervical Cancer; Head and Neck Squamous Cell Carcinoma
• Intervention / Treatment: Drug: HPV E6-specific TCR-T cells

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Qingzhu Jia; Phone Number: +8615223334184 +8615223334184; Email: jiaqingzhu0801@outlook.com

Study Locations

• China
  • Chongqing
    • Chongqing, Chongqing, China, 400037
      • Recruiting
      • Qingzhu Jia
      • Contact: Qingzhu Jia; Phone Number: +8615223334184 +8615223334184; Email: jiaqingzhu0801@outlook.com

Participation Criteria

Eligibility Criteria

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

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: Xinqiao Hospital of Chongqing
• Collaborators: TCRCure Biopharma Ltd.
• Investigators: Principal Investigator: Bo Zhu, Oncology of Department, Xinqiao Hospital

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2018
• Primary Completion (Anticipated): August 30, 2020
• Study Completion (Anticipated): August 30, 2021

Study Registration Dates

• First Submitted: May 28, 2018
• First Submitted That Met QC Criteria: June 24, 2018
• First Posted (Actual): July 6, 2018

Study Record Updates

• Last Update Posted (Actual): May 1, 2019
• Last Update Submitted That Met QC Criteria: April 29, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Cervical Diseases; Uterine Diseases; Head and Neck Neoplasms; Carcinoma, Squamous Cell; Uterine Cervical Neoplasms; Carcinoma; Squamous Cell Carcinoma of Head and Neck
• Other Study ID Numbers: XQDC20180520

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No