CompletedPhase 2

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

France82 participantsStarted 2018-11-06

Plain-language summary

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.

Who can participate

Age range18 Years

SexALL

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Inclusion Criteria: * Cytologically or histologically proven stage IV NSCLC * Patients who had received first-line platin salt-based chemotherapy and will be given second-line nivolumab; * Patients with bone metastases, symptomatic or not, confirmed by X-rays, CT scan, MRI, PET-CT scan or technetium bone scintigraphy * Presence of at least 1 measurable target lesion, according to RECIST criteria 1.1, in a non-irradiated site * For non-squamous cell NSCLC, patients without known activating epidermal growth factor receptor mutation, anaplastic lymphoma kinase (ALK) or reactive oxygen species (ROS)-1 translocation, or B-Raf proto-oncogene, serine/threonine kinase (BRAF V600) mutation * PD-L1 status known and expressed as a percentage of tumor cells; assessed at the diagnosis or the more recent PD-L1 expression status available. * Eastern Cooperative Oncology Group Performance Status 0/1 * Estimated life-expectancy ≥12 weeks * No prior malignant tumor during the previous 5 years, except for in situ carcinomas of the cervix or basal or squamous cell carcinomas of the skin adequately treated; * Adequate organ function determined by laboratory analyses less than 7 days before inclusion: * Normal hepatic function: bilirubin \< 1.5× normal (N), alanine aminotransferase and aspartate aminotransferase \<2.5× N or \<5× N if hepatic metastases are present * Renal function (renal clearance of creatinine at least ≥45 mL/min) * Hematological function: absolute number of neutrophils ≥…

What they're measuring

Overall Response Rate (ORR) according to the PD-L1-expression rate (threshold set at 1%)

Timeframe: At 24 months

Trial details

NCT IDNCT03669523

SponsorCentre Hospitalier Annecy Genevois

Sponsor typeOTHER

Study typeINTERVENTIONAL

Primary completion2023-10-19