This study is a single-arm, dose-escalation, investigator-initiated exploratory clinical trial designed to evaluate the tolerability, safety, pharmacokinetic profile, and preliminary efficacy of MT027 Cell Injection in patients with advanced primary or secondary peritoneal tumors.
This study evaluates the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary efficacy of intrathecal or intracerebroventricular (ICV) injection of MT027 in glioma treatment. Partial clinical data have been presented at the 2024 ASCO Annual Meeting. Dose Groups: Three predefined dose levels: 1×10⁷ cells/dose、3×10⁷ cells/dose、6×10⁷ cells/dose. Administration frequency: Every 2 weeks (with a 4-week dose-limiting toxicity \[DLT\] observation period after the first injection, followed by subsequent injections every 2 weeks). Dose Escalation: Accelerated titration + 3+3 design: First dose cohort: Accelerated titration strategy. Subsequent cohorts: Standard "3+3" dose-escalation. Dose Adjustment: After reaching predefined dose levels, if no DLT or significant safety events occur, dose escalation decisions (including MTD determination) will be jointly reviewed by investigators and collaborators based on integrated safety and efficacy data. Primary Objectives: To assess the safety, tolerability, and determine the maximum tolerated dose (MTD) of MT027 cell injection in patients with advanced primary or secondary peritoneal tumors.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
10
D-10 to D-2: Fludarabine (25 mg/m2/day) will be administered intravenously for 3 days;D-10 to D-2: Cyclophosphamide (250 mg/m2/day) will be administered intravenously for 3 days.
Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
Shanghai, Shanghai Municipality, China
RECRUITINGAdverse Events (AEs)
Incidence and severity of adverse events.
Time frame: 2 years
Serious Adverse Events (SAEs)
Incidence and severity of serious adverse events.
Time frame: 2 years
Adverse Events of Special Interest (AESI)
Adverse Events of Special Interest (AESI)(Incidence and severity ) Incidence and severity of adverse event of special interest.
Time frame: 2 years
Identification of Maximum Tolerated Dose (MTD) & Incidence of Dose-limiting Toxicities (DLTs)
Incidence and severity of dose-limiting toxicities (DLTs) following infusion of CAR-T cell injection, at each dose level tested in dose escalation phase.
Time frame: 4 weeks after the CAR-T cells infusion
Objective Response Rate (ORR)
The Objective Response Rate (ORR) is the percentage of participants who achieved Complete Response (CR) or Partial Response (PR) based on RECIST version 1.1.
Time frame: 2 years
Disease Control Rate (DCR)
Disease control rate (DCR) is the percentage of participants who achieved Complete Response (CR) or Partial Response (PR) or Stable disease (SD) based on RECIST version 1.1.
Time frame: 2 years
Duration of Overall Response (DOR)
Time from documentation of disease response to disease progression.
Time frame: 2 years
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Progression-Free Survival (PFS)
PFS is defined as the time from CAR-T infusion to the date of the disease progression or death from any cause.
Time frame: 2 years
Overall Survival (OS)
OS is defined as the time from CAR-T infusion to the date of death due to any cause.
Time frame: 2 years
Bio-distribution of Anti mesothelin CAR-T cells
CAR copies will be measured by qPCR to evaluate the expansion and persistenc e of CAR-T cells in vivo. Cmax, Tmax, AUC0-tlast and AUC0-inf of CAR copies will be analyzed. Cmax is the maximum CAR level in peripheral blood or bone marrow. Tmax is time to peak CAR level in blood or bone marrow. AUC0-tlast and AUC0-inf are area under the curve of the CAR level in blood .
Time frame: 2 years
Cytokine Level in Peripheral Blood
Level of cytokines in serum.
Time frame: 2 years
Anti-drug Antibodies
Number of participants with anti-drug antibodies.
Time frame: 2 years
RP2D
The RP2D is the optimal dose level selected for further evaluation in Phase II clinical trials, based on safety, tolerability, pharmacokinetic (PK), pharmacodynamic (PD), and preliminary efficacy data gathered during Phase I dose-escalation studies. It represents the dose that balances maximum therapeutic benefit with acceptable toxicity for patients.
Time frame: 4 weeks after the CAR-T cells infusion