Bronchial Artery Chemoembolization (BACE) Combination Therapy for Advanced NSCLC

Overview

Patients with advanced non-small cell lung cancer (NSCLC) who experience disease progression after standard systemic therapies or are unable to tolerate such therapies have limited subsequent treatment options. Bronchial arterial chemoembolization (BACE) is a locoregional interventional procedure that delivers chemotherapeutic agents directly into tumor-feeding bronchial arteries, followed by arterial embolization, with the aim of increasing local drug exposure and reducing tumor blood supply. This prospective, open-label, single-arm Phase II study will evaluate the efficacy and safety of BACE-based combination therapy in adult patients with advanced NSCLC who have no remaining standard treatment options and whose target intrathoracic lesions are considered suitable for BACE. Approximately 20 eligible participants are planned for enrollment between April 2026 and April 2028. All enrolled participants will receive protocol-specified BACE in combination with systemic anti-tumor therapy. Treatment selection and administration will be performed according to the study protocol, taking into account the participant's molecular characteristics, prior treatments, clinical condition, and treatment tolerance. The study will primarily assess local tumor control and the safety of the combined treatment strategy. Tumor response and disease progression will be evaluated by contrast-enhanced imaging according to RECIST criteria, and adverse events will be assessed using CTCAE Version 5.0. Additional assessments will include objective tumor response, disease control, progression-free survival, and overall survival. Exploratory analyses will investigate the systemic pharmacokinetics of chemotherapeutic agents administered during BACE and potential treatment-related changes in the tumor immune microenvironment.

This prospective, open-label, single-arm Phase II study is designed to investigate BACE-based combination therapy in patients with advanced non-small cell lung cancer who have exhausted, progressed after, or are unable to tolerate available standard systemic treatments. The study focuses on patients with clinically relevant intrathoracic tumor lesions that remain technically suitable for bronchial arterial intervention. BACE is intended to provide concentrated locoregional treatment to lung tumors through the bronchial arterial circulation. During the procedure, tumor-feeding bronchial arteries will be identified by angiography and selectively catheterized in accordance with the protocol. Protocol-specified chemotherapeutic agents will then be administered through the target arteries, followed by embolization of the tumor-feeding vessels. This approach is intended to increase drug exposure within the tumor while reducing arterial blood supply and inducing tumor ischemia and necrosis. BACE will be administered in combination with protocol-defined systemic anti-tumor treatment. The systemic treatment include chemotherapy, immune checkpoint inhibition, targeted therapy, or another protocol-permitted regimen, as appropriate for the participant's tumor molecular profile, previous treatment history, organ function, clinical condition, and prior treatment tolerance. The timing and administration of systemic therapy in relation to BACE will follow the study protocol. There is no control group or placebo treatment in this study. Before treatment, participants will undergo protocol-specified baseline clinical, laboratory, and imaging assessments. Contrast-enhanced chest computed tomography will be used to document measurable intrathoracic lesions and establish the baseline tumor burden. Follow-up imaging will be performed at protocol-defined intervals to evaluate changes in target lung lesions and overall disease status according to RECIST criteria. Local progression of the treated intrathoracic lesions will be distinguished from progression occurring at other pulmonary or extrapulmonary sites. Safety monitoring will cover both procedure-related complications and toxicities associated with the combined systemic treatment. Clinical symptoms, laboratory abnormalities, imaging findings, and adverse events will be evaluated throughout treatment and during the protocol-defined safety follow-up period. Adverse events will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0. Investigators will assess the relationship of each adverse event to BACE, embolization, intra-arterial chemotherapy, and concomitant systemic anti-tumor therapy. Participants will be followed for local tumor status, overall disease progression, subsequent anti-tumor treatments, and survival. The study is intended to determine whether BACE-based combination therapy can provide clinically meaningful local tumor control with an acceptable safety profile in this heavily pretreated population. The study also includes exploratory pharmacokinetic and translational research. Peripheral venous blood samples will be collected at protocol-defined time points within 72 hours after BACE to characterize the systemic exposure to chemotherapeutic agents administered through the bronchial arteries. Serial biospecimens collected at baseline, before BACE, and during follow-up will be used to investigate treatment-related changes in local and systemic immune status. These analyses will explore whether ischemia, tumor necrosis, and locoregional drug delivery induced by BACE are associated with changes in the tumor immune microenvironment and whether potential immune biomarkers correlate with treatment response or prognosis. Time-to-event variables will be summarized using Kaplan-Meier methods. Tumor response proportions will be reported with exact two-sided confidence intervals, and safety findings will be summarized descriptively. Pharmacokinetic and biomarker analyses are exploratory and will primarily use descriptive methods without formal confirmatory hypothesis testing.