Clinical trial NCT04139057: EBV-Specific Anti-PD1 TCR-T Cells in the Treatment of EBV-Positive NHSCC
Official title: Single-Arm Trial of EBV-Specific TCR-T Cells With Anti-PD1 Auto-secreted Element in the Treatment of EBV-Positive Head and Neck Carcinoma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Head and Neck Squamous Cell Carcinoma
Lead sponsor: Xinqiao Hospital of Chongqing
Sponsor class: OTHER
Collaborators: name: TCRCure Biopharma Ltd.
First posted: 2019-10-25
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Epstein-Barr virus (EBV) infections is known to be a high-risk factor to induce nasopharyngeal cancers. To date, EBV-related head and neck squamous cell carcinoma (HNSCC) is still a major concern in east Asia, especially in China. Concurrent therapies for HNSCC have limited response rate and high chance of relapse. However, EBV-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 EBV 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 EBV positive HNSCC, 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: The Maximum Tolerated Dose
timeFrame: 8 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: ChongQing
country: China
facility: Department of Oncology, Xinqiao Hospital
state: Chongqing
Study officials:
affiliation: Army Medical University, China
name: Bo Zhu, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: