Actively Recruiting
The Efficacy and Safety of Narlumosbart in Combination With Stereotactic Body Radiation Therapy to Improve the Efficacy of First-line Chemotherapy Combined With Immunotherapy in Patients With Bone Metastases From Advanced Non-small Cell Lung Cancer
Led by Fudan University · Updated on 2026-03-20
27
Participants Needed
1
Research Sites
197 weeks
Total Duration
On this page
AI-Summary
What this Trial Is About
Introduction: Immunotherapy in combination with chemotherapy have been recommended as the first-line treatment of driver-negative advanced non-small cell lung cancer (NSCLC), but the efficacy is worse in NSCLC patients with bone metastases due to the immunosuppressive microenvironment. Studies have shown that not only the nuclear factor kappa-B ligand (RANKL) inhibitors but also Stereotactic Body Radiation Therapy (SBRT) play a significant role in improving the tumor immune microenvironment. Therefore, narlumosbart，a monoclonal antibody (mAb) targeting RANKL，in combination with SBRT may have synergistic effects and improve efficacy of immunotherapy and chemotherapy in driver-negative advanced NSCLC patients with bone metastases. Methods: This single-arm, single-center phase II clinical trial will enroll NSCLC patients with bone metastases who have not received any systemic therapy. Patients will receive narlumosbart and bone target lesion SBRT in combination with first-line treatment immunotherapy and chemotherapy after screening eligible subjects. Narlumosbart, 120mg/time, subcutaneous injection, is administered every 4 weeks. For the treatment of SBRT for bone metastases, the dose of 24Gy/3F is used for spinal metastases, and 30Gy/5F or 35Gy/5F is used for non-spinal lesions. Chemotherapy combined with immune checkpoint inhibitor therapy was used in accordance with the guidelines. The primary endpoint is to assess the objective response rate of NSCLC patients with bone metastases from narlumosbart combined with SBRT and first-line chemotherapy and immunotherapy. The secondary endpoints include progression-free survival, overall survival and safety. Sample size calculation used the Simon Two-Stage method. 9 patients will be enrolled in the first stage. If ≥ 2 patients achieve CR/PR, the second stage of enrollment will be performed. If only 2 patients \< achieve CR/PR, the trial will be terminated. In the second phase, 15 patients will be enrolled. 27 subjects will be enrolled in this project, considering the dropout rate of 10%. Wangjun Yan AND Zhengfei Zhu are the Co-Principal Investigators of this study.
CONDITIONS
Official Title
The Efficacy and Safety of Narlumosbart in Combination With Stereotactic Body Radiation Therapy to Improve the Efficacy of First-line Chemotherapy Combined With Immunotherapy in Patients With Bone Metastases From Advanced Non-small Cell Lung Cancer
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Signed written informed consent before starting any trial procedures
- Age between 18 and 80 years
- Confirmed stage IV non-small cell lung cancer by histology or cytology
- Confirmed bone metastasis requiring local radiotherapy treatment
- No prior systemic treatment for lung cancer including chemotherapy, targeted therapy, or immunotherapy
- Adenocarcinoma patients must be negative for driver genes EGFR, ALK, and ROS-1; squamous cell carcinoma patients do not require genetic testing
- At least one measurable lesion other than bone metastases, including lymph nodes
- Bone metastases not treated or requiring local treatment other than the radiotherapy lesion
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Expected survival time longer than 3 months
- Adequate organ function based on specific laboratory tests including blood counts, liver and kidney function, coagulation, and thyroid function
- Negative pregnancy test for women of childbearing potential before treatment
- Use of effective contraception for men and women during treatment and for 120 days after last dose
You will not qualify if you...
- Diagnosis of small cell lung cancer or mixed small cell and non-small cell lung cancer
- Lesion is isolated and can be treated with curative intent
- Need for surgical treatment after study evaluation
- Bone radiotherapy lesion previously treated or unsuitable for radiotherapy
- Presence of active brain metastases
- Other cancers diagnosed within 5 years except certain skin cancers and carcinoma in situ
- Participation in other clinical trials or use of investigational drugs/devices within 4 weeks before treatment
- Prior treatment with anti-PD-1, anti-PD-L1, anti-PD-L2, other T cell receptor-targeting agents, or RANKL-targeting drugs
- Active autoimmune disease requiring systemic therapy within 2 years
- Uncontrolled pleural or ascites effusions requiring frequent drainage
- History of organ transplantation except corneal or stem cell transplantation
- Active bone metabolism diseases or uncontrolled thyroid disorders
- Allergy to study drugs or their components
- Unresolved toxicity from previous treatments greater than grade 1 except fatigue or hair loss
- Known HIV infection
- Untreated active hepatitis B
- Hypocalcemia not improved with treatment
- Current or history of jaw bone infections or surgeries affecting healing
- Use of certain anti-bone agents within 6 months
- Recent vaccination with live vaccine within 30 days
- Pregnant or breastfeeding women
- Serious or uncontrolled systemic diseases including severe heart conditions, recent heart attack, uncontrolled blood pressure, lung disease, infections, liver disease, poorly controlled diabetes, significant proteinuria, or mental disorders preventing cooperation
- Any condition that may interfere with study participation or results as judged by the investigator
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Trial Site Locations
Total: 1 location
1
Fudan University Shanghai Cancer Center
Shanghai, Shanghai Municipality, China
Actively Recruiting
Research Team
Z
Zhengfei Zhu
CONTACT
W
Wangjun Yan
CONTACT
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NA
Model
SINGLE_GROUP
Primary Purpose
TREATMENT
Number of Arms
1
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