Phase 2 N=226 Randomized Double-blind Treatment

Denosumab in Combination With Chemotherapy as First-line Treatment of Metastatic Non-small Cell Lung Cancer

Non-Small Cell Lung Cancer

Bottom Line

View on ClinicalTrials.gov: NCT01951586 ↗

Enrolled (actual)

226

Serious AEs

89.1%

Results posted

Aug 2017

Primary outcome: Primary: Overall Survival (OS) — 10.9; 10.7 months — p=0.5157

Study Design & Population

Study type: Interventional
Phase: Phase 2
Interventions: Denosumab (Drug); Zoledronic acid (Drug); Placebo to Denosumab (Drug); Standard Chemotherapy (Drug); Placebo to Zoledronic Acid (Drug)
Age: Adult, Older Adult · 18+ yrs
Sex: All
Sponsor: Amgen
Primary completion: Jul 2016

Outcome Measures

Outcome	Result	p-value
PRIMARY Overall Survival (OS)	10.9; 10.7	0.5157
SECONDARY Correlation of Tumor Tissue RANK Expression With Overall Survival	0.84; 1.00; 0.72; 0.92; 0.80; 1.00	0.3759
SECONDARY Correlation of Tumor Tissue RANK Ligand Expression With Overall Survival	0.77; 0.93; 0.79; 0.93	0.3946
SECONDARY Objective Response Rate	43.4; 36.8	0.3491
SECONDARY Correlation of Tumor Tissue RANK Expression With Objective Response Rate	1.00; 0.88; 1.18; 0.82; 1.16; 0.88	0.4760
SECONDARY Correlation of Tumor Tissue RANKL Expression With Objective Response Rate	1.27; 1.10; 1.25; 1.09	0.4671
SECONDARY Clinical Benefit Rate	53.9; 47.9	0.4654
SECONDARY Progression-free Survival (PFS)	5.7; 5.2	0.7363
SECONDARY Serum Denosumab Trough Levels in Participants Who Received Q3W Dosing	8590; 12200; 19700; 19600; 22800; 24300	—
SECONDARY Serum Denosumab Trough Levels in Participants Who Received Q4W Dosing	8990; 10900; 15700; 14500; 13000; 15400	—
SECONDARY Number of Participants With Treatment-emergent Adverse Events	76; 144; 68; 129; 6; 20	—

Summary

This randomized phase 2 trial is studying the effect of adding denosumab to standard chemotherapy in the treatment of advanced lung cancer.

Eligibility Criteria

Inclusion Criteria

Histologically or cytologically confirmed stage IV non-small cell lung carcinoma (NSCLC), according to 7th Tumor/Node/Metastasis (TNM) classification (cytological specimens obtained by bronchial washing or brushing, or fine-needle aspiration are acceptable)
Subject has available and has provided consent to release to the sponsor (or designee) a tumor block with confirmed tumor content (or approximately 20 unstained charged slides [a minimum of 7 slides is mandatory]) and the corresponding pathology report
Planned to receive 4 to 6 cycles of pemetrexed or gemcitabine in combination with cisplatin or carboplatin
For subjects to receive pemetrexed, planned to receive vitamin B12 and folate per pemetrexed approved labeling
Radiographically evaluable (measurable or non-measurable) disease (according to modified Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria
Other inclusion criteria may apply

Exclusion Criteria

Known presence of documented sensitizing epidermal growth factor receptor (EGFR) activating mutation or echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) translocation (screening following local standards, but strongly encouraged in non-squamous histology)
Known brain metastases (systematic screening of patients not mandatory)
Any prior systemic therapy (before randomization) for the treatment of NSCLC (including chemoradiation), except if for non-metastatic disease and was completed at least 6 months prior to randomization
Planned to receive bevacizumab
Significant dental/oral disease, including prior history or current evidence of osteonecrosis/ osteomyelitis of the jaw, or with the following:
Active dental or jaw condition which requires oral surgery
Non-healed dental/oral surgery
Planned invasive dental procedures for the course of the study.

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT01951586). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.