Bronchial Artery Chemoembolization (BACE) Combination Therapy for Advanced NSCLC

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.

Inclusion criteria

• Age between 18 and 75 years old; Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0-2.
• Histopathologically confirmed advanced non-small cell lung cancer (NSCLC), with at least one measurable target lesion defined by RECIST Version 1.1.
• Two eligible patient subgroups:

Patients with negative driver gene alterations: experienced disease progression or intolerable toxicity after platinum-based doublet chemotherapy combined with PD-1/PD-L1 immune checkpoint inhibitors; Patients with positive driver gene mutations (e.g., EGFR, ALK): experienced disease progression or unacceptable adverse reactions after corresponding targeted therapy plus at least one line of systemic chemotherapy.

• Target lung lesions are suitable for bronchial arterial chemoembolization (BACE), as assessed by interventional radiology specialists.
• Adequate function of major vital organs.
• Able to provide written informed consent prior to any study-related procedures.

Exclusion criteria

• Histopathological confirmation of mixed small cell lung cancer components.
• Active bleeding or coagulation disorders.
• Severe hypersensitivity to contrast media, chemotherapeutic agents, or combined study medications.
• Extensive and rapidly progressive intra-pulmonary or extra-pulmonary metastatic lesions.
• Angiography during the procedure shows that superselective catheterization cannot completely avoid hazardous blood vessels such as spinal arteries.
• Severe pre-existing hepatic, renal, cardiac, or pulmonary dysfunction.
• Estimated survival time less than 3 months.