NCT03669523: DENIVOS

Denosumab and Nivolumab Combination As 2d-line Therapy in Stage IV NSC Lung Cancer with Bone Metastases (DENIVOS)

Completed Phase 2 Last updated 13 February 2025

What this trial tests

Phase 2 trial testing Denosumab-nivolumab combination in Carcinoma, Non-Small-Cell Lung in 82 participants. Completed in 19 October 2023.

Timeline

6 November 2018

Primary endpoint
19 October 2023

19 October 2023

Quick facts

Lead sponsor	Centre Hospitalier Annecy Genevois
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	82
Start date	6 November 2018
Primary completion	19 October 2023
Estimated completion	19 October 2023
Sites	27 locations across France

Drugs / interventions tested

• Denosumab-nivolumab combination — full drug profile →

Conditions studied

• Carcinoma, Non-Small-Cell Lung — all drugs for Carcinoma, Non-Small-Cell Lung →
• Bone Metastases — all drugs for Bone Metastases →

Sponsor

Centre Hospitalier Annecy Genevois

Who can join

18 and older, any sex, with Carcinoma, Non-Small-Cell Lung or Bone Metastases. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

Bone metastases are common in Non-Small Cell Lung Cancer (NSCLC). They most often occur during disease progression. It is thought that more than half of the patients with bone metastases will have at least 1 skeletal-related event (SRE, i.e. pathological fractures, medullary compression, analgesic radiotherapy, preventive and/or analgesic surgery and hypercalcemia).

Expert and medical Society guidelines, notably European Society for Medical Oncology in 2014, then in 2016, recommended using anti-resorptive agents (bisphosphonates or denosumab) to prevent SREs, attenuate pain and improve the quality of life, and decrease the medical-economic impact of this major metastatic site. Denosumab was accorded marketing authorization in France in 2011 as an anti-resorptive agent for bone metastases to delay the occurrence of SREs in lung-cancer patients.

Immunotherapy, notably immune-checkpoint inhibitors, like nivolumab (anti-programed death-1), has recently become an integral part of the therapeutic arsenal against NSCLCs. Nivolumab was accorded marketing authorization based on the phase III CHECKMATE 017 (squamous cell NSCLCs) and CHECKMATE 057 (non-squamous cell NSCLCs) trials versus docetaxel, after the phase II CHECKMATE 063 trial.

The denosumab-nivolumab combination is commonly used in current practice but has not been evaluated prospectively. The aim of this trial is to evaluate the combination of denosumab and nivolumab in second line of NSCLC with bone metastases.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Improvement of the anticancer efficacy of PD-1/PD-L1 blockade via combination therapy and PD-L1 regulation.
   Wu M, Huang Q, Xie Y, Wu X, et al · · 2022 · cited 336× · PMID 35279217 · DOI 10.1186/s13045-022-01242-2
2. Targeting strategies for bone diseases: signaling pathways and clinical studies.
   Xu H, Wang W, Liu X, Huang W, et al · · 2023 · cited 97× · PMID 37198232 · DOI 10.1038/s41392-023-01467-8
3. Resistance to immune checkpoint inhibitors in non-small cell lung cancer: biomarkers and therapeutic strategies.
   Walsh RJ, Soo RA. · · 2020 · cited 77× · PMID 32670423 · DOI 10.1177/1758835920937902
4. Bone metastases in non-small cell lung cancer: a narrative review.
   Knapp BJ, Devarakonda S, Govindan R. · · 2022 · cited 43× · PMID 35693589 · DOI 10.21037/jtd-21-1502
5. Immune Checkpoint Inhibitor Therapy for Bone Metastases: Specific Microenvironment and Current Situation.
   Liu C, Wang M, Xu C, Li B, et al · · 2021 · cited 42× · PMID 34877360 · DOI 10.1155/2021/8970173
6. Predictive and Prognostic Biomarkers for Lung Cancer Bone Metastasis and Their Therapeutic Value.
   Chai X, Yinwang E, Wang Z, Wang Z, et al · · 2021 · cited 36× · PMID 34722241 · DOI 10.3389/fonc.2021.692788
7. Efficacy and safety of concomitant immunotherapy and denosumab in patients with advanced non-small cell lung cancer carrying bone metastases: A retrospective chart review.
   Li HS, Lei SY, Li JL, Xing PY, et al · · 2022 · cited 22× · PMID 36105807 · DOI 10.3389/fimmu.2022.908436
8. Biological and Clinical Aspects of Metastatic Spinal Tumors.
   Litak J, Czyżewski W, Szymoniuk M, Sakwa L, et al · · 2022 · cited 17× · PMID 36230523 · DOI 10.3390/cancers14194599