Clinical trial NCT05587543: Clinical Study on the EBV CAR-T /TCR-T Cells in the Treatment of Nasopharyngeal Carcinoma
Official title: Clinical Study on the Safety and Efficacy of EBV CAR-T /TCR-T Cells in the Treatment of Recurrent / Refractory EBV Positive Nasopharyngeal Carcinoma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: EARLY_PHASE1
Conditions: Nasopharyngeal Carcinoma
Lead sponsor: Fudan University
Sponsor class: OTHER
First posted: 2022-10-20
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: CAR-T、TCR-T
Primary purpose: TREATMENT

Brief summary: This study was a single-arm, open-label, "3 + 3" dose-escalation Exploratory research. The patients were divided into two groups: EBV TCR-T-cell Group and EBV CAR-T-cell group. The EBV CAR-T-treated group received three progressively increasing dose levels (3.0 × 106 cells/kg, 9.0 × 106 cells/kg, 1.5 × 107 cells/kg) of EBV CAR-T-cell therapy; The EBV TCR-T-cell group received three progressively increasing doses (5.0 × 106 cells/kg, 1.5 × 107 cells/kg, 3.0 × 107 cells/kg) of EBV TCR-T-cell therapy.

Detailed description: Each subject was observed for at least 4 weeks after cell reinfusion (DLT observation period) . A minimum of three participants should be included in each dose group, and two or more participants should not be included in each dose group at the same time, each subject should not be enrolled until the first 1 subject did not experience a grade 3 or higher adverse event (CTCAE5.0) related to the study drug during the DLT observation period. Three or six subjects were enrolled in each dose group, depending on the occurrence of DLT. If three subjects in one dose group did not experience DLT, three subjects were enrolled in the next higher dose group; if one of three subjects experienced DLT, three more subjects were enrolled in the dose group; Expanded to 6 subjects; if only 1 of the 6 subjects after amplification produced a DLT, then 3 subjects were enrolled into the next higher dose; If a DLT occurred in ≥2 of the 6 subjects after amplification, then the dose was specified to be higher than the MTD (MTD defined as the highest dose at which a DLT occurred in ≤1/6 subjects) , new subjects were included in the previous lower dose (tolerated dose) group until the lower dose group reached 6 subjects. If DLT occurred in ≤1/6 of the subjects, the lower dose group was defined as MTD or the best effective dose. A total of six subjects received the maximum tolerated dose. In the course of the study, the researcher can combine the safety and preliminary efficacy data of the enrolled subjects, and take the safety of the subjects and the maximum benefit of the disease as the premise, study treatment was performed at the maximum tolerated dose or other doses determined by the investigator.

Eligibility criteria: Inclusion Criteria:

* Voluntary written informed consent;
* Age ≥18 years old, ≤75 years old, male and female;
* Expected survival ≥3 months;
* The Eastern Cooperative Oncology Group (ECOG) physical fitness score was 0-2;
* Ebv-positive nasopharyngeal carcinoma was diagnosed by in situ hybridization with Ebers (Eber-fish) .
* Pathological Paraffin section testing (within 5 years before signing the informed consent form) ;
* At least one measurable lesion according to RECIST v1.1 criteria for solid tumors;
* Recurrent/metastatic nasopharyngeal carcinoma patients who had previously failed second-line or more systemic therapy;
* An apheresis or venous access can be established and there are no other contraindications to blood cell isolation；
* CTCAE 5.0 was lower than grade 1 in the side effects of previous anti-tumor therapy (radiotherapy, chemotherapy, targeted therapy, etc.)
* During the study period and up to 6 months after the end of the administration, fertile subjects -LRB-both male and female) were required to use effective medical contraception. For women of reproductive age, a pregnancy test should be performed within 72 hours before the first dose, and the results were negative.

Exclusion Criteria:

* Active central nervous system metastases (except those that are stable after treatment)；
* HIV positive, HBsAg positive and HBV DNA copy number positive (quantitative detection ≥1000 CPS/ml) , HCV antibody positive and HCV RNA positive;
* Patients with mental or psychological disorders who can not cooperate with the treatment and evaluation of the curative effect;
* Subjects with severe autoimmune disease and long-term use of immunosuppressants;
* Active or uncontrolled infection requiring systemic therapy was present within 14 days prior to enrollment；
* Any unstable systemic disease;
* Complicated with dysfunction of important organs such as lung, brain and kidney.
* Subjects had undergone major surgery or severe trauma within 4 weeks before receiving cell therapy, or were expected to undergo major surgery during the study period.
* Participants received their last dose of radiation or anti-tumor therapy within 4 weeks of receiving the cell therapy.
* Participants had or had had other cancers that were incurable for up to 3 years, except for cervical cancer in situ or skin basal-cell carcinoma, and other cancers that had disease-free survival of more than 5 years.
* Treated with Chimeric antigen receptor t-cell therapy within six months.
* Graft-versus-host disease (GVHD)；
* Subjects who were receiving systemic steroid therapy before screening and who required long-term systemic steroid therapy during treatment as determined by the investigator (with the exception of inhaled or topical use) ; And subjects treated with systemic steroids within 72 hours before cell reinfusion (except for inhalation or topical use) .
* Severe allergies or a history of allergies;
* Subjects requiring anticoagulant therapy;
* Pregnant or lactating women, or a six-month pregnancy plan (for both men and women)；
* Researchers believe there are other reasons not to include people in treatment.

Primary outcomes:
measure: Dose Limiting Toxicities
timeFrame: one year
measure: MTD or the best effective dose
timeFrame: one year
measure: Incidence of AE、SAE、AESI
timeFrame: one year
Secondary outcomes:
measure: PK parameter：Cmax
timeFrame: one year
measure: PK parameter：Tmax
timeFrame: one year
measure: ORR
timeFrame: one year
measure: DCR
timeFrame: one year
measure: DOR
timeFrame: one year
measure: PFS
timeFrame: one year
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Fudan University
Study officials:
affiliation: Fudan University
name: Dongmei Ji, Doctorate
role: PRINCIPAL_INVESTIGATOR
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