NCT03774732

PD-1 Inhibitor and Chemotherapy With Concurrent Irradiation at Varied Tumour Sites in Advanced Non-small Cell Lung Cancer

• Status: Active Not Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 327 (estimated)
• Sponsor: UNICANCER · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Overall survival (OS) of patients with advanced (stage IIIB/IV) non-small-cell lung cancer (NSCLC) remains short after the first line of treatment with a median OS of 12.2 months in non squamous NSCLC and 9.2 months in squamous NSCLC . In this setting the programmed death 1/ligand 1 (PD-1/-L1) were targeted with nivolumab (IgG4) in advanced squamous and nonsquamous NSCLC leading to an increase of the 1-year OS rate of approximately 10-15% in both histologies. Nivolumab, pembrolizumab and atezolizumab are now considered a standard of care in 2nd line advanced NSCLC and in 1st line for pembrolizumab but but prognosis still remains poor in advanced NSCLC. Overall survival (OS) of patients with advanced (stage III/IV) NSCLC remains limited with a median OS of 12.2 months in non-squamous NSCLC and 9.2 months in squamous NSCLC if anti-PD1 alone. It is of around 16 months if pembrolizumab is combined with chemotherapy. Preclinical data indicates that anti-tumor efficacy is increased when anti-PD-1/-L1 are combined with irradiation (IR). Radiotherapy alone can elicit tumor cell death which can increase tumor antigen in the blood stream, favoring recognition by the immune system and its activation against tumor cells outside of the radiation field (="abscopal effect"). IR may also reverse acquired resistance to PD-1 blockade immunotherapy by limiting T-cell exhaustion. Because of these preclinical and clinical data several studies analysing the combination of IR and anti-PD1 in NSCLC are ongoing. Among them, two studies are testing the administration of IR and nivolumab in stage III NSCLC: the NCT02768558 phase III trial (RTOG), and the NCT02434081 phase II trial (ETOP). Antonia et al \[2017\] tested the use of anti-PD-L1 after chemoradiotherapy in unresectable stage III NSCLC. Median time to distant metastasis was increased (23.2 months vs. 14.6 months, p\<0.001). An increase of OS is consequently expected. However, no study involving concurrent RT and pembrolizumab combined with chemotherapy in advanced NSCLC is ongoing, which is the purpose of the present study, NIRVANA-Lung.

Conditions

• Non Small Cell Lung Cancer
• Non Small Cell Lung Cancer Metastatic
• Non-Small Cell Carcinoma of Lung, TNM Stage 4

Interventions

Type	Name	Description
RADIATION	Radiotherapy	Irradiation technique (3D-CRT or SABR) will be at physician discretion.
DRUG	Pembrolizumab	pembrolizumab will be administered as per standard of care every 3 weeks until progression or toxicity
DRUG	Chemotherapy	for squamous NSCLC carboplatin AUC6, paclitaxel 200 mg/m² every 3 weeks for 4 cycles; for non-squamous NSCLC carboplatin AUC5 or cisplatin 75 mg/m² every 3 weeks for 4 cycles, and pemetrexed 500 mg/m² every 3 weeks until progression or toxicity

Timeline

• Start date: 2018-01-24
• Primary completion: 2026-12-22
• Completion: 2026-12-22
• First posted: 2018-12-13
• Last updated: 2026-02-25

Locations

58 sites across 2 countries: France, Monaco