Tislelizumab Plus Chemotherapy and BACE for Unresectable NSCLC

Official title

Tislelizumab Combined With Intravenous Chemotherapy and Bronchial Artery Chemoembolization as Conversion Therapy for Unresectable Non-Small Cell Lung Cancer: A Multicenter, Single-Arm, Phase II Trial (BEACON-Lung)

Overview

The goal of this phase 2 trial is to evaluate the efficacy and safety of tislelizumab combined with intravenous chemotherapy and bronchial artery chemoembolization (BACE) as conversion therapy for patients with initially unresectable stage IIIA-IIIB non-small cell lung cancer (NSCLC). The main questions it aims to answer are: * What is the 1-year event-free survival (EFS) rate with this treatment? * Can this treatment improve tumor response and the chance of curative-intent resection? * What adverse events occur during treatment? Participants will receive tislelizumab, intravenous chemotherapy, and BACE for up to 4 cycles. Tumor response and resectability will be evaluated by imaging and multidisciplinary team (MDT) assessment every 2 cycles. Participants who become resectable may undergo surgery followed by postoperative treatment per protocol. Participants who remain unresectable after 4 cycles will receive guideline-recommended chemoradiotherapy followed by tislelizumab consolidation. Regular follow-up will be performed for efficacy and safety assessment.

Interventions

• Drug Tislelizumab
  Tislelizumab 200 mg is administered intravenously on Day 0 of each 21-day cycle for up to 4 cycles. Postoperative or consolidation tislelizumab may be given according to protocol-defined treatment pathways.
• Drug Intravenous Chemotherapy
  Intravenous chemotherapy is administered on Day 1 of each 21-day cycle for up to 4 cycles. Patients with lung squamous cell carcinoma receive albumin-bound paclitaxel, and patients with lung adenocarcinoma receive pemetrexed. Carboplatin is administered intra-arterially during BACE in cycles with the procedure; if BACE is not performed in a given cycle, carboplatin is administered intravenously on the same day per protocol.
• Procedure Bronchial Artery Chemoembolization (BACE)
  BACE is performed on Day 1 of the first 21-day treatment cycle using intra-arterial carboplatin infusion followed by embolization with 300-500 μm blank microspheres. Subsequent BACE procedures are performed on demand, based on tumor response on contrast-enhanced chest CT and multidisciplinary team (MDT) evaluation. The total number of BACE procedures ranges from 1 to 4.

Primary outcome measures

• 1-Year Event-Free Survival (EFS) Rate [Time frame: 1 year after the first dose of study treatment]

Secondary outcome measures (7)

• R0 Resection Rate [Time frame: Up to approximately 20 weeks after the first dose of study treatment]
• Objective Response Rate (ORR) [Time frame: Up to approximately 30 months after the first dose of study treatment.]
• Pathologic Complete Response (pCR) Rate [Time frame: At the time of surgery, up to approximately 20 weeks after the first dose of study treatment.]
• Major Pathologic Response (MPR) Rate [Time frame: At the time of surgery, up to approximately 20 weeks after the first dose of study treatment.]
• Event-Free Survival (EFS) [Time frame: From the first dose of study treatment up to approximately 30 months]
• Overall Survival (OS) [Time frame: From the first dose of study treatment up to approximately 30 months.]
• Incidence of Adverse Events [Time frame: From the first dose of study treatment up to approximately 30 months.]

Eligibility criteria

Inclusion criteria

• Age 18 to 80 years
• Histologically or cytologically confirmed non-small cell lung cancer (NSCLC)
• Newly diagnosed, previously untreated stage IIIA-IIIB NSCLC according to the 9th edition TNM staging system
• Initially unresectable disease as determined by multidisciplinary team (MDT) assessment
• At least 1 measurable intrapulmonary lesion according to RECIST version 1.1
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Forced expiratory volume in the first second (FEV1) > 1.0 L and > 40% of predicted normal value
• Estimated life expectancy of at least 3 months
• Adequate organ function
• Willingness to provide tumor tissue for pathology, molecular testing, and PD-L1 assessment before enrollment
• Women of childbearing potential must have a negative pregnancy test within 72 hours before the first dose and agree to use effective contraception during the study and for 3 months after the last dose of tislelizumab
• Men with partners of childbearing potential must agree to use effective contraception during the study and for 3 months after the last dose of tislelizumab
• Ability to understand and willingness to sign a written informed consent form

Exclusion criteria

• Prior local therapy for NSCLC, including radiotherapy or interventional therapy
• Known positive driver genomic alterations, including EGFR mutations, ALK rearrangements, ROS1 rearrangements, and MET exon 14 skipping alterations
• Distant organ metastasis
• History of another malignancy within the past 5 years
• Active autoimmune disease or history of autoimmune disease requiring systemic treatment
• Known allergy to any study drug or excipient
• Interstitial lung disease, non-infectious pneumonitis, chronic obstructive pulmonary disease, or other uncontrolled systemic diseases judged to interfere with study treatment
• Severe chronic or active infection requiring systemic antibacterial, antifungal, or antiviral therapy, including active tuberculosis
• Major surgery requiring general anesthesia within 4 weeks before first dose
• Any medical condition, alcohol or drug abuse, or dependence that may interfere with study treatment, interpretation of results, or increase treatment risk
• Participation in another interventional therapeutic clinical study
• Psychiatric illness or history of psychotropic drug abuse that may compromise study participation
• Any condition judged by the investigator to make the patient unsuitable for the study

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Sichuan Cancer Hospital and Research Institute — Chengdu

Publications

• Liu B, Zhou J, He W, Zhang R, Cheng X, Xu L, Xie B, Liang Y, Guo S. Bronchial artery infusion of PD-1 inhibitors plus chemotherapy improves progression-free survival in advanced NSCLC: a prospective cohort study. Sci Rep. 2026 Feb 3;16(1):7067. doi: 10.1038/s41598-026-37607-7. PMID 41634290
• Zheng L, Zhang D, Zhang Y, Chen L, Chen W, Huang C, Zhu L, Fang S, Weng Q, Chen M, Tu J, Zhao Z, Ji J. Efficacy and safety of bronchial artery chemoembolization combined with chemotherapy and immune checkpoint inhibitors for advanced lung squamous cell carcinoma. Eur J Med Res. 2026 Feb 12. doi: 10.1186/s40001-026-03979-9. Online ahead of print. PMID 41680955
• Liang C, Han D, Li H, Wang M, Kuang D, Chen H, Miao H, Chen P, Lu H, Jiao P, Ren J, Han X, Li F, Duan X. Bronchial Arterial Chemoembolization Combined with Tislelizumab for Non-Small Cell Lung Cancer: An Exploratory, Prospective, Single-Arm, Phase II Trial. J Vasc Interv Radiol. 2026 Apr;37(4):108001. doi: 10.1016/j.jvir.2026.108001. Epub 2026 Jan 16. PMID 41548595
• Xiang J, Lan W, Cai D, Wang Y, Li W, Tu J, Huang J. Clinical outcomes, toxic effect, and immune microenvironment changes of drug-eluting bead bronchial arterial chemoembolisation/bronchial arterial chemoembolization combined with immunotherapy in treating elderly patients with non-small cell lung cancer. Clin Radiol. 2025 May;84:106849. doi: 10.1016/j.crad.2025.106849. Epub 2025 Feb 13. PMID 40068253
• Sheng J, Luo H, Liu X, Liu C, Zhou W, Zhao Y, Liu R, Li D, Xu C, Yang B, Liu Y, Fu X, Bao L, Wang K, Hao J, Liu W. Tislelizumab (anti-PD-1) plus chemotherapy as neoadjuvant therapy for patients with stage IB3/IIA2 cervical cancer (NATIC): a prospective, single-arm, phase II study. Signal Transduct Target Ther. 2025 Jul 4;10(1):215. doi: 10.1038/s41392-025-02294-9. PMID 40615377
• Zhou Q, Pan Y, Yang X, Zhao Y, Han G, Pang Q, Zhang Z, Wang Q, Yao J, Wang H, Yang W, Liu B, Chen Q, Du X, Cai K, Li B, Huang Y, Li X, Song L, Shi W, Wu YL. Neoadjuvant SHR-1701 with or without chemotherapy in unresectable stage III non-small-cell lung cancer: A proof-of-concept, phase 2 trial. Cancer Cell. 2024 Jul 8;42(7):1258-1267.e2. doi: 10.1016/j.ccell.2024.05.024. Epub 2024 Jun 20. PMID 38906157
• Sorin M, Prosty C, Ghaleb L, Nie K, Katergi K, Shahzad MH, Dube LR, Atallah A, Swaby A, Dankner M, Crump T, Walsh LA, Fiset PO, Sepesi B, Forde PM, Cascone T, Provencio M, Spicer JD. Neoadjuvant Chemoimmunotherapy for NSCLC: A Systematic Review and Meta-Analysis. JAMA Oncol. 2024 May 1;10(5):621-633. doi: 10.1001/jamaoncol.2024.0057. PMID 38512301
• Rami-Porta R, Nishimura KK, Giroux DJ, Detterbeck F, Cardillo G, Edwards JG, Fong KM, Giuliani M, Huang J, Kernstine KH Sr, Marom EM, Nicholson AG, Van Schil PE, Travis WD, Tsao MS, Watanabe SI, Rusch VW, Asamura H; Members of the IASLC Staging and Prognostic Factors Committee and of the Advisory Boards, and Participating Institutions. The International Association for the Study of Lung Cancer Lun PMID 38447919

Identifiers

NCT: NCT07561983 · KY-2025-346-03

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗