Efficacy and safety of narlumosbart in combination with stereotactic body radiation therapy followed by first-line chemotherapy combined with immunotherapy in advanced driver gene-negative non-small cell lung cancer patients with bone metastases: a p
Jin Li, Nianlan Zhou, Saiquan Lu, Xi Yang, Wangjun Yan, Zhengfei Zhu, Mo ChengIntroduction
Immunotherapy in combination with chemotherapy has been recommended as the first-line treatment of driver gene-negative advanced non-small cell lung cancer (NSCLC), but the efficacy is reduced in NSCLC patients with bone metastases due to the immunosuppressive microenvironment. Both nuclear factor kappa-B ligand (RANKL) inhibitors and stereotactic body radiation therapy (SBRT) have been shown to modulate the tumour immune microenvironment. Therefore, narlumosbart, a monoclonal antibody targeting RANKL, in combination with SBRT, may exert synergistic effects and improve efficacy of first-line chemoimmunotherapy in this population.
Methods and analysis
This single-arm, single-centre phase II clinical trial will enrol driver gene-negative advanced NSCLC patients with bone metastases who have not received any systemic therapy. Eligible patients will receive narlumosbart (120 mg subcutaneously every 4 weeks) and SBRT to bone target lesions (24 Gy/3 fractions for spinal metastases and 30–35 Gy/5 fractions for non-spinal lesions), followed by standard first-line chemoimmunotherapy. The primary endpoint is the objective response rate of non-radiotherapy lesions. Secondary endpoints include safety and tolerability, progression-free survival, overall survival, bone-related events, pain score and quality of life. Sample size was calculated using the Simon’s Two-Stage method (α=0.05, power=0.8, H₀=25%, H₁=50%). Nine patients will be enrolled in stage 1. If ≥2 patients achieve complete response (CR)/partial response (PR), an additional 15 patients will be enrolled in stage 2. If fewer than two patients achieve CR/PR, the trial will be terminated. 27 subjects will be enrolled in this project, considering the dropout rate of 10%.
Ethics and dissemination
This study was approved by the Medical Ethics Committee of Fudan University Shanghai Cancer Center (approval number 2411308–15) on 6 December 2024. The trial registration number is