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Clinical Trial Results:
A randomised, open-label phase III trial evaluating the addition of denosumab to standard first-line anticancer treatment in advanced NSCLC

Summary
EudraCT number	2013-003156-21
Trial protocol	BE IT IE DE GB AT ES SI PL
Global end of trial date	29 Feb 2020

Results information
Results version number	v1(current)
This version publication date	25 Sep 2021
First version publication date	25 Sep 2021
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
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Trial information

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Sponsor protocol code

ETOP_5-12/EORTC_08111

ISRCTN number

US NCT number

NCT02129699

WHO universal trial number (UTN)

Other trial identifiers

Amgen number: 20080166

Sponsor organisation name

European Thoracic Oncology Platform

Sponsor organisation address

Effingerstrasse 40, Bern, Switzerland, 3008

Public contact

ETOP Coordinating Office, ETOP , +41 31389 93 91, SPLENDOUR@etop-eu.org

Scientific contact

ETOP Coordinating Office, ETOP , +41 31389 93 91, SPLENDOUR@etop-eu.org

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

01 Mar 2019

Is this the analysis of the primary completion data?

Yes

Primary completion date

06 Apr 2018

Global end of trial reached?

Yes

Global end of trial date

29 Feb 2020

Was the trial ended prematurely?

Yes

Main objective of the trial

To evaluate whether the addition of denosumab to standard firstline chemotherapy in advanced NSCLC improves overall survival.

Protection of trial subjects

The responsible investigator ensured that this study was conducted in agreement with either the Declaration of Helsinki (available on the World Medical Association web site (http://www.wma.net)) and/or the laws and regulations of the country, whichever provides the greatest protection of the patient. The protocol had been written, and the study was conducted according to the ICH Harmonized Tripartite Guideline on Good Clinical Practice (ICH-GCP, available online at http://www.ema.europa.eu/pdfs/human/ich/013595en.pdf). The protocol was approved by the competent ethics committee(s) as required by the applicable national legislation.

Background therapy

All patients will receive standard, platinum-based doublet chemotherapy combined with pemetrexed or gemcitabine for first-line NSCLC. The number of cycles of doublet chemotherapy will be between 4 and 6 cycles, according to the institution’s policy. Similarly, pemetrexed or erlotinib maintenance treatment after doublet chemotherapy is allowed in both arms.

Evidence for comparator

Denosumab is a fully human monoclonal IgG2 antibody binding with a high affinity to RANKL. It is specific and does not demonstrate significant binding to other members of the TNF ligand superfamily. As a result of its specific mechanism of action on the bone matrix, denosumab has become a new option for the treatment of osteoporosis [Aeschlimann et al Cell Death Differ 2004]. In breast cancer, denosumab was demonstrated superior to zoledronic acid in delaying time to first on-study SRE (hazard ratio, 0.82; 95% CI, 0.71 to 0.95; P = .01 superiority), associated with a greater reduction in bone turnover markers. Overall survival, disease progression, and rates of adverse events were similar between groups [Stopeck et al J Clin Oncol 2010]. In a pivotal phase 3 trial in patients with solid tumours and multiple myeloma (other than breast or prostate) and bone metastasis, denosumab was shown to be non-inferior – with a trend toward superiority – to zoledronic acid in delaying time to first SRE (HR, 0.84; 95% CI, 0.71 to 0.98; P= .0007, representing 16% reduction in hazard). Regarding NSCLC, the effect of denosumab on time to first on-study SRE relative to zoledronic acid by tumour stratification factors resulted in an HR of 0.84 for NSCLC (95% CI, 0.64 to 1.10; P=0.20) [Henry et al. J Clin Oncol 2011].

Actual start date of recruitment

01 Aug 2014

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country