Combining PD-1 immunotherapy, denosumab, and chemotherapy for advanced non-squamous lung cancer without targetable mutations

A Phase II Single-Arm Study Evaluating the Efficacy of PD-1 Inhibitor Combined With Denosumab and Chemotherapy in Locally Advanced or Metastatic Non-Squamous Non-Small Cell Lung Cancer Patients With Driver Gene-Negative Status

Phase 2 Interventional China Medical University, China · NCT07034391

This trial will test whether adding a PD-1 immunotherapy and denosumab to standard chemotherapy helps people with advanced non-squamous non-small cell lung cancer who do not have targetable driver mutations.

Quick facts

PhasePhase 2
Study typeInterventional
Enrollment40 (estimated)
Ages18 Years to 75 Years
SexAll
SponsorChina Medical University, China Academic / other
Drugs / interventionsdenosumab, chemotherapy, immunotherapy
Locations1 site (Shenyang, Liaoning)
Trial IDNCT07034391 on ClinicalTrials.gov

What this trial studies

This Phase 2 interventional trial gives participants a PD-1/PD-L1 inhibitor together with denosumab and standard chemotherapy to see how well the combination controls locally advanced or metastatic non-squamous NSCLC that lacks common driver mutations. Eligible patients have no prior systemic therapy for advanced disease, measurable disease by RECIST v1.1, ECOG performance status 0-1, and adequate organ function. The trial will monitor tumor responses, disease control, and safety/tolerability during treatment. Outcomes will compare response rates and adverse events to historical expectations for chemotherapy plus immunotherapy.

Who should consider this trial

Good fit: Adults with histologically confirmed locally advanced or metastatic non-squamous NSCLC who are negative for EGFR/ALK/ROS1/BRAFV600E/RET/METex14 mutations, have not received prior systemic therapy for advanced disease, have measurable disease, ECOG 0-1, and adequate organ and marrow function are the intended participants.

Not a fit: Patients with targetable driver mutations, prior systemic therapy for advanced NSCLC, mixed small-cell/non-small-cell histology, prior use of denosumab or other bone-modifying agents, or poor performance status are unlikely to benefit from this regimen.

Why it matters

Potential benefit: If successful, the combination could improve tumor response and disease control for patients without targetable mutations compared with chemotherapy alone.

How similar studies have performed: PD-1 inhibitors combined with chemotherapy have shown benefit in many prior trials, but adding denosumab as an immune-modulating or supportive agent is less tested and remains relatively novel.

Eligibility criteria

Show full inclusion / exclusion criteria
Inclusion Criteria:

* Histologically or cytologically confirmed locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC)
* Documented negative for EGFR/ALK/ROS1/BRAFV600E/RET/METex14 mutations by validated genomic testing, with no prior targeted therapy and no history of other malignancies
* No previous systemic therapy for advanced/metastatic disease
* At least one measurable lesion per RECIST v1.1
* Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1
* No use of parathyroid hormone/derivatives, calcitonin, osteoprotegerin, mithramycin, or potassium supplements within the past 6 months
* Adequate organ and marrow function

Exclusion Criteria:

* Histologically or cytologically confirmed combined small cell and non-small cell lung cancer (mixed histology)
* Any previous systemic anticancer treatment for NSCLC, including chemotherapy, biologics, immunotherapy, or investigational agents
* Prior use of denosumab or any bone-modifying agents (e.g., bisphosphonates)
* Uncontrolled hypocalcemia or hypophosphatemia
* History or current evidence of osteonecrosis of the jaw (ONJ) or osteomyelitis of the jaw

Where this trial is running

Shenyang, Liaoning

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
Conditions Non-Small Cell Lung Cancer
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.