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RECRUITING
NCT05477927
PHASE1

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

Sponsor: Sichuan University

View on ClinicalTrials.gov

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.

Official title: A Phase I, Open-label, Single-arm, Dose-escalation and Expansion Study of Dual-targeting VEGFR1 and PD-L1 CAR-T Cells in Patients With Pleural, Peritoneal, or Leptomeningeal Metastases From Solid Tumors

Key Details

Gender

All

Age Range

18 Years - 80 Years

Study Type

INTERVENTIONAL

Enrollment

40

Start Date

2023-02-15

Completion Date

2028-12-31

Last Updated

2026-08-13

Healthy Volunteers

No

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.

Locations (1)

West China Hospital, Sichuan University

Chengdu, Sichuan, China