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Dual-targeting VEGFR1 and PD-L1 CAR-T for Pleural, Peritoneal, or Leptomeningeal Metastases

NCT05477927 · Status: RECRUITING · Phase: PHASE1 · Type: INTERVENTIONAL · Enrollment: 40

Last updated 2026-08-13

No results posted yet for this study

Summary

This is a Phase I, open-label, single-arm, dose-escalation and expansion study designed to evaluate the safety, tolerability, and preliminary antitumor activity of dual-targeting VEGFR1/PD-L1 chimeric antigen receptor (CAR) T-cells in patients with solid tumors presenting with pleural, peritoneal, or leptomeningeal metastases.

Despite advances in systemic therapies, patients with serosal cavity and leptomeningeal dissemination face extremely poor prognoses and limited treatment options due to the unique immunosuppressive tumor microenvironment and the physical barrier of these anatomical sites. Preclinical evidence suggests that simultaneous blockade of VEGFR1-mediated angiogenesis and PD-L1-mediated immune checkpoint signaling via a bispecific CAR-T construct may synergistically overcome local immunosuppression and enhance tumor eradication in these sanctuary sites.

The study consists of two phases: a dose-escalation phase utilizing a standard 3+3 design and backfilling design to determine the maximum tolerated dose (MTD) or recommended phase II dose (RP2D) of locoregionally administered CAR-T cells, followed by a dose-expansion phase to further assess safety and preliminary efficacy at the RP2D.

Eligible patients will receive a single infusion of VEGFR1/PD-L1 dual-CAR T-cells via intrapleural, intraperitoneal, or intrathecal routes, depending on the primary site of metastasis. The primary endpoints are the incidence of dose-limiting toxicities (DLTs) and treatment-emergent adverse events (TEAEs) graded by CTCAE v5.0. Secondary endpoints include objective response rate (ORR) , progression-free survival (PFS), overall survival (OS), and assessment of CAR-T cell persistence and cytokine profiles in peripheral blood and local effusion fluids.

Conditions

  • Malignant Peritoneal Effusion
  • Malignant Ascites
  • Serous Cavity Metastatises
  • Leptomeningeal Metastases

Interventions

BIOLOGICAL

Dual-targeting VEGFR1/PD-L1 CAR-T cells

Autologous T cells genetically engineered to express a chimeric antigen receptor targeting both VEGFR1 and PD-L1. Cells are administered via locoregional routes.

Sponsors & Collaborators

  • Sichuan University

    lead OTHER

Principal Investigators

  • Yongsheng Wang, Prof. · West China Hospital

Study Design

Allocation
NA
Purpose
TREATMENT
Masking
NONE
Model
SINGLE_GROUP

Eligibility

Min Age
18 Years
Max Age
80 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2023-02-15
Primary Completion
2027-06-30
Completion
2028-12-31

Countries

  • China

Study Locations

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Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT05477927 on ClinicalTrials.gov