This is an open-label, single-arm phase I dose-escalation study designed to evaluate the safety, tolerability, pharmacokinetic profile, and preliminary efficacy of MT027 in patients with advanced primary peritoneal malignancies or abdominal metastases secondary to malignant solid tumors. The study primarily focuses on determining the maximum tolerated dose and recommended phase II dose through sequential cohort dose escalation, while secondarily characterizing the pharmacokinetic parameters and collecting initial efficacy data regarding tumor response. This investigation comprehensively evaluates the pharmacodynamic and pharmacokinetic profile of MT027 cellular therapy through three primary objectives: (1) systematic monitoring of treatment-emergent adverse events and clinically significant laboratory parameter deviations; (2) assessment of antitumor activity with correlative biomarker analysis; and (3) characterization of cellular kinetics including biodistribution patterns, mechanistic pathways of therapeutic activity, and comprehensive immunogenicity assessment measuring both cellular/humoral immune responses against MT027 cells. The protocol further investigates potential host-versus-product immune reactions through longitudinal monitoring of donor-specific antibodies and cytokine release profiles, while employing advanced molecular tracking methodologies to elucidate cellular persistence and functional modulation within the tumor microenvironment.
This single-arm, dose-escalation phase I clinical trial aims to assess the tolerability, safety, pharmacokinetic profile, and preliminary efficacy of MT027 in patients with advanced primary peritoneal malignancies or secondary abdominopelvic metastatic solid tumors. This phase I study implements a tripartite dose-escalation framework (1×10⁷, 3×10⁷, and 6×10⁷ cells/administration) with biweekly intravenous dosing. Post-initial dosing requires a 4-week observation period for dose-limiting toxicities (DLT) graded per NCI-CTCAE v5.0 criteria, followed by subsequent 14-day interval administrations. Following 6 completed treatment cycles (12 weeks), participants may either transition to surveillance follow-up or continue therapy per investigator-determined risk-benefit analysis. The hybrid accelerated titration "3+3" design initiates with single-patient cohorts for preliminary dose evaluation, transitioning to conventional 3+3 methodology (minimum 3 patients/cohort) for subsequent dose levels. Protocol-defined dose escalation beyond predetermined thresholds requires documented consensus between investigators and sponsors, contingent upon comprehensive review of cumulative safety parameters (including DLT absence) and emerging efficacy indicators. The trial progresses through sequential Phase IA (dose-finding) and Phase IB (dose-expansion) stages. Phase Ia cessation triggers include either confirmation of Recommended Phase II Dose (RP2D) or investigator-verified favorable therapeutic index at any dose level. An interim analysis will be conducted upon Phase IA completion, followed by submission of an ethical amendment application prior to initiating Phase IB. Phase IB will be initiated with multi-cohort expansion (n=9-18 per cohort) across prespecified malignancies: colorectal adenocarcinoma (CRC), gastric carcinoma (GC), high-grade serous ovarian carcinoma (HGSOC), breast cancer (BC), non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), metastatic castration-resistant prostate cancer (mCRPC), clear cell renal cell carcinoma (ccRCC), and cervical squamous cell carcinoma (CSCC), etc.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
12
Prior to MT027 cell infusion, lymphodepleting chemotherapy with fludarabine and cyclophosphamide was administered. Dose Group 1: 1×10⁷ cells per administration; Dose Group 1: 3×10⁷ cells per administration; Dose Group 1: 6×10⁷ cells per administration; Based on the data obtained, adjustments to the specific number of cells in the established dosage groups and/or the addition of dosage groups may be made after discussion between the collaborators and researchers. A dose reduction titration may also be conducted based on the completed dosage groups.
The First Affiliated Hospital Zhejiang University School of Medicine
Hangzhou, Zhejiang, China
RECRUITINGIncidence of Adverse events after MT027 cells infusion
Incidence and proportion of adverse events during the trial (NCI-CTCAE v5.0 criteria )
Time frame: 28 days
Obtain the maximum tolerated dose of MT027 cells
Dose-limiting toxicity after cell infusion
Time frame: 3 months
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
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
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
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
Overall Survival Rate (OSR)
Time frame: 2 years
Progression-Free Survival Rate (PFSR)
Time frame: 2 years
Puncture-Free Survival (PuFS)
Time frame: 2 years
Objective Response Rate of peritoneal cavity effusion
Time frame: 2 years
Symptoms and signs of peritoneal cavity effusion
Time frame: 2 years
Bio-distribution of MT027 cells
The pharmacokinetic (PK) parameters will be calculated by measuring CAR copy numbers of MT027 cells in ascites and peripheral blood following single-dose and multiple-dose administrations, including: Single-dose PK metrics: Area under the curve from 0 to 28 days (AUC\<sub\>0-28d\</sub\>), peak concentration (C\<sub\>max\</sub\>), time to peak concentration (T\<sub\>max\</sub\>), and elimination half-life (T\<sub\>1/2\</sub\>); Steady-state PK parameters during and post-multiple dosing: Trough concentration at steady state (C\<sub\>min,ss\</sub\>), peak concentration at steady state (C\<sub\>max,ss\</sub\>), average steady-state concentration (C\<sub\>av,ss\</sub\>), fluctuation index (DF), area under the curve over a dosing interval at steady state (AUC\<sub\>0-τ\</sub\>), time to peak concentration at steady state (T\<sub\>max,ss\</sub\>), accumulation ratio (R\<sub\>ac\</sub\>), and persistence profile.
Time frame: 3 months
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