NCT06912152

MT027 in Patients With Advanced Peritoneal Malignancies or Abdominal Metastatic Solid Tumors

Phase I Dose-Escalation Study of MT027: Evaluating Tolerability, Safety, Pharmacokinetics, and Preliminary Efficacy in Patients With Advanced Peritoneal Malignancies or Abdominal Metastatic Solid Tumors

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 12 (estimated)
• Sponsor: Zhejiang University · Academic / Other
• Sex: All
• Age: 18 Years – 70 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

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.

Conditions

• B7-H3-positive Advanced Malignant Solid Tumors Advanced Primary Peritoneal Tumors or Secondary Abdominal Metastatic Malignant Solid Tumors

Interventions

Type	Name	Description
BIOLOGICAL	MT027 CAR-T cells	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.

Timeline

• Start date: 2025-05-12
• Primary completion: 2028-10-31
• Completion: 2028-12-31
• First posted: 2025-04-04
• Last updated: 2025-05-21

Locations

1 site across 1 country: China