Immunotherapy combined with chemotherapy is recommended as first-line treatment for advanced driver gene–negative non-small cell lung cancer (NSCLC). However, patients with bone metastases often experience reduced efficacy of chemoimmunotherapy, attributed in the protocol to an immunosuppressive microenvironment within bone lesions.
Both inhibition of the receptor activator of nuclear factor kappa-B ligand (RANKL) and stereotactic body radiation therapy (SBRT) have been reported to modulate tumour immune biology. The trial protocol hypothesizes that administering narlumosbart, a monoclonal antibody targeting RANKL, together with SBRT to bone metastases may produce synergistic effects that enhance the systemic activity of subsequent first-line chemoimmunotherapy in this population.
This is a single-arm, single-centre phase II clinical trial enrolling patients with advanced, driver gene–negative NSCLC who have bone metastases and have not received any prior systemic therapy. The protocol specifies that written informed consent will be obtained from all participants prior to enrolment.
Key eligibility criteria reported in the source are limited to the disease characteristics described above (driver gene–negative advanced NSCLC with bone metastases, treatment-naïve for systemic therapy). The source does not provide additional inclusion or exclusion criteria in this summary.
Eligible patients will receive narlumosbart administered subcutaneously at a dose of 120 mg every 4 weeks. Concurrently, SBRT will be delivered to bone target lesions with the following dose-fractionation schemes:
The protocol describes this combination (narlumosbart plus SBRT) as a lead-in treatment prior to initiating standard first-line chemoimmunotherapy.
After the narlumosbart plus SBRT lead-in, patients will proceed to standard first-line chemoimmunotherapy for driver gene–negative advanced NSCLC. The source summary does not detail specific chemotherapy agents, immunotherapy agents, or regimens; it only states that standard first-line chemoimmunotherapy will be administered following the investigational lead-in.
Primary endpoint
Secondary endpoints
These endpoints are described in the source protocol summary; the document does not supply detailed definitions, assessment schedules, or response criteria in this brief report.
Sample size and interim design
The sample size was calculated using Simon’s two-stage design with a one-sided α = 0.05 and power = 0.8, comparing a null ORR of 25% (H0) versus an alternative ORR of 50% (H1). The two-stage plan is:
Accounting for an anticipated 10% dropout rate, the protocol plans to enroll a total of 27 subjects for the study.
The source does not provide additional statistical analysis plans, censoring rules, or subgroup analyses in this summary.
Ethics approval
This study was approved by the Medical Ethics Committee of Fudan University Shanghai Cancer Center (approval number 2411308 - 15) on 6 December 2024. The protocol states that the trial will be conducted in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines.
Registration and sponsorship
The trial is registered on ClinicalTrials.gov with identifier NCT06738160 and is sponsored by Fudan University. Registration occurred in December 2024 prior to enrolment of the first participant, and the first participant enrolment is reported to have begun in February 2025 in the source summary.
Consent and participant protections
Written informed consent will be obtained from all participants prior to enrolment. The source indicates that results will be published in a peer-reviewed journal, but does not specify timelines or data-sharing plans in this summary.
The protocol states that trial results will be submitted for publication in a peer-reviewed journal. No additional dissemination details, such as planned conference presentations or public data release, are provided in the source summary.
This phase II, single-arm protocol evaluates whether a lead-in strategy of narlumosbart (RANKL inhibition) combined with SBRT to bone metastases can improve systemic objective responses to subsequent first-line chemoimmunotherapy in patients with driver gene–negative advanced NSCLC and bone involvement. The trial uses a Simon two-stage design with clearly stated stopping rules and plans for safety and efficacy assessment. Further methodological details, specific systemic regimens, and response-assessment schedules were not reported in the provided source summary.