Clinical trial NCT03578406: HPV-E6-Specific Anti-PD1 TCR-T Cells in the Treatment of HPV-Positive NHSCC or Cervical Cancer
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Cervical Cancer
Head and Neck Squamous Cell Carcinoma
Lead sponsor: Xinqiao Hospital of Chongqing
Sponsor class: OTHER
Collaborators: name: TCRCure Biopharma Ltd.
First posted: 2018-07-06
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: To Determine the Maximum Tolerated Dose
timeFrame: 8 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Chongqing
country: China
facility: Qingzhu Jia
state: Chongqing
Study officials:
affiliation: Oncology of Department, Xinqiao Hospital
name: Bo Zhu
role: PRINCIPAL_INVESTIGATOR
References: