LMP2-Specific IL12-secreting TCR-T Cells in the Treatment of EBV-Positive Metastatic/Refractory Nasopharyngeal Carcinoma

• ClinicalTrials.gov Identifier: NCT04509726
• Recruitment Status: Not yet recruiting
• First Posted: August 12, 2020
• Last Update Posted: August 12, 2020
• Sponsor: Xinqiao Hospital of Chongqing
• Collaborator: TCRCure Biopharma Ltd
• Information provided by (Responsible Party): Qingzhu Jia, M.D., Xinqiao Hospital of Chongqing

Study Description

Brief Summary:

Epstein-Barr virus (EBV) infections is known to be a high-risk factor to induce cervical cancers. To date, EBV-related nasopharyngeal carcinoma (NPC) is still a major concern in east Asia, especially in China. Concurrent therapies for NPC 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 LMP2-epitope 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. Interleukin 12 (IL-12) seemed to represent the ideal candidate for tumor immunotherapy, due to its ability to activate both innate (NK cells) and adaptive (cytotoxic T lymphocytes) immunities. several clinical studies have been initiated in which IL-12 is applied as an adjuvant in cancer vaccines, in gene therapy including locoregional injections of IL-12 plasmid and in the form of tumor-targeting immunocytokines (IL-12 fused to monoclonal antibodies). Therefore, TCR-T cells armed with a IL12-secretion element could further enhance the efficacy of TCR-T in solid cancers.

Condition or disease	Intervention/treatment	Phase
Nasopharyngeal Carcinoma	Drug: LMBP2-specific TCR-T cell with IL12 auto-secreting element	Phase 1; Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 20 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Single-Arm Trial of LMP2-Specific TCR-T Cells With IL12 Auto-secreted Element in the Treatment of EBV-Positive Head and Neck Carcinoma Metastatic/Refractory Nasopharyngeal Carcinoma
• Estimated Study Start Date: September 2020
• Estimated Primary Completion Date: August 2021
• Estimated Study Completion Date: August 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: EBV TCR-T	Drug: LMBP2-specific TCR-T cell with IL12 auto-secreting element; Patients were pre-conditioned with chemotherapy and infused with LBMP2-specific TCR-T cells with IL12 auto-secreting element

Outcome Measures

Primary Outcome Measures :

1. The Maximum Tolerated Dose [ Time Frame: 8 weeks ]
   Verify the MTD of TCR-T cells for LMP2 antigen for treatment. The first nine patients enrolled in this project will be infused in a dose-climbing approach, with every three patients as a group. The first group of patients returned to 5e+6/kg TCR-T cells, the second group returned to 1e+7/kg TCR-T cells, and the third group returned to 5e+7/kg TCR-T cells. The remaining 11 patients will infused with TCR-Ts in the maximum tolerated dose

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 EBV positive NPC, 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

Locations

China, Chongqing

Department of Oncology, Xinqiao Hospital

ChongQing, Chongqing, China, 400037

Sponsors and Collaborators

Xinqiao Hospital of Chongqing

TCRCure Biopharma Ltd

More Information

• Responsible Party: Qingzhu Jia, M.D., Doctor, Xinqiao Hospital of Chongqing
• ClinicalTrials.gov Identifier: NCT04509726
• Other Study ID Numbers: XQDC20200801
• First Posted: August 12, 2020
• Last Update Posted: August 12, 2020
• Last Verified: August 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

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

Additional relevant MeSH terms:

Carcinoma; Nasopharyngeal Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Nasopharyngeal Neoplasms; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases