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

Tracking Information

• First Submitted Date: August 10, 2020
• First Posted Date: August 12, 2020
• Last Update Posted Date: August 12, 2020
• Estimated Study Start Date: September 2020
• Estimated Primary Completion Date: August 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 10, 2020)

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

• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: LMP2-Specific IL12-secreting TCR-T Cells in the Treatment of EBV-Positive Metastatic/Refractory Nasopharyngeal Carcinoma
• 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Nasopharyngeal Carcinoma

Intervention

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

Study Arms

Experimental: EBV TCR-T

Intervention: Drug: LMBP2-specific TCR-T cell with IL12 auto-secreting element

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Not yet recruiting
• Estimated Enrollment (submitted: August 10, 2020): 20
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: August 2023
• Estimated Primary Completion Date: August 2021 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 70 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Listed Location Countries: China

Administrative Information

• NCT Number: NCT04509726
• Other Study ID Numbers: XQDC20200801
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

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

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Responsible Party: Qingzhu Jia, M.D., Xinqiao Hospital of Chongqing
• Study Sponsor: Xinqiao Hospital of Chongqing
• Collaborators: TCRCure Biopharma Ltd
• Investigators: Not Provided
• PRS Account: Xinqiao Hospital of Chongqing
• Verification Date: August 2020