Serous Cavity Metastatises

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.