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

NCT03774732 · Status: ACTIVE_NOT_RECRUITING · Phase: PHASE3 · Type: INTERVENTIONAL · Enrollment: 327

Last updated 2026-02-25

No results posted yet for this study

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

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

Sponsors & Collaborators

  • National Cancer Institute, France

    collaborator OTHER_GOV

  • UNICANCER

    lead OTHER

Principal Investigators

  • Jérôme DOYEN, MD · Centre Antoine Lacassagne

  • Antonin LEVY, MD · Gustave Roussy, Cancer Campus, Grand Paris

  • Benjamin BESSE, MD · Gustave Roussy, Cancer Campus, Grand Paris

Study Design

Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Model
PARALLEL

Eligibility

Min Age
18 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2018-01-24
Primary Completion
2026-12-22
Completion
2026-12-22

Countries

  • France
  • Monaco

Study Locations

More Related Trials

Entities

Drugs

Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT03774732 on ClinicalTrials.gov