--- title: "Phase II Trial of Narlumosbart plus SBRT before Chemoimmunotherapy in Driver Gene–Negative NSCLC w" id: "bmj-open-3-efficacy-and-safety-of-narlumosbart-in-combination-with-stereotactic-body" canonical_url: "https://medichelpline.com/clinical-feed/bmj-open-3-efficacy-and-safety-of-narlumosbart-in-combination-with-stereotactic-body" content_type: "clinical_feed_article" specialty: "Oncology" source_name: "BMJ Open" source_url: "http://bmjopen.bmj.com/cgi/content/short/16/10/e120892?rss=1" published_at: "2026-10-01T11:56:34.000Z" evidence_level: "Journal Feed" license: "CC-BY-NC-4.0 / Informational Use" --- # Phase II Trial of Narlumosbart plus SBRT before Chemoimmunotherapy in Driver Gene–Negative NSCLC w ## Provenance & Clinical Metadata - **Canonical URL:** https://medichelpline.com/clinical-feed/bmj-open-3-efficacy-and-safety-of-narlumosbart-in-combination-with-stereotactic-body - **Specialty:** [Oncology](https://medichelpline.com/clinical-feed/oncology.md) - **Primary Source:** BMJ Open - **Source URL:** [Original Journal Publication](http://bmjopen.bmj.com/cgi/content/short/16/10/e120892?rss=1) - **Published At:** 2026-10-01T11:56:34.000Z - **Evidence Rating:** Journal Feed ## Executive GIST (TL;DR) - Advanced driver gene–negative non-small cell lung cancer (NSCLC) patients with bone metastases have reduced efficacy from standard first-line **chemoimmunotherapy**, likely due to an immunosuppressive bone tumour microenvironment. - Both **RANKL** inhibition and **stereotactic body radiation therapy (SBRT)** can modulate the tumour immune microenvironment; combining these modalities may enhance systemic anti-tumour immune responses. - This is a single-arm, single-centre phase II study enrolling previously untreated, driver gene–negative advanced NSCLC patients with bone metastases to receive **narlumosbart** (120 mg SC every 4 weeks) plus SBRT to bone lesions, followed by standard first-line chemoimmunotherapy. - SBRT regimen: 24 Gy in 3 fractions for spinal metastases; 30–35 Gy in 5 fractions for non-spinal bone lesions. - Primary endpoint: objective response rate (ORR) of non-radiotherapy lesions. Key secondary endpoints: safety/tolerability, progression-free survival (PFS), overall survival (OS), bone-related events, pain score, and quality of life. - Sample size uses Simon’s two-stage design (α = 0.05, power = 0.8) with H0 = 25% and H1 = 50%: stage 1 enrolls 9 patients; if ≥2 achieve CR/PR, stage 2 adds 15 patients. Total planned enrollment is 27 accounting for a 10% dropout. If fewer than 2 responses in stage 1, the trial stops. - The study received ethics approval from Fudan University Shanghai Cancer Center (approval number 2411308 - 15) on 6 December 2024 and is registered at ClinicalTrials.gov (NCT06738160). Written informed consent will be obtained and results will be published in a peer-reviewed journal. ## Clinical Analysis & Structured Key Points Introduction 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 NCT06738160 at clinicaltrials.gov, sponsored by Fudan University, and registered in December 2024 before the enrolment of the first participant in February 2025. The trial will be conducted in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines. Written informed consent will be obtained from all participants prior to enrolment. 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