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Non Small Cell Lung CancerPhase 3NIRVANA-LUNGNCT03774732

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

A Phase 3 study testing Radiotherapy, Pembrolizumab and Chemotherapy in people with Non Small Cell Lung Cancer and Non Small Cell Lung Cancer Metastatic, run by UNICANCER at 58 sites in 2 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial 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 . Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Radiotherapy, Pembrolizumab and Chemotherapy
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
327 participants
Where
58 sitesin 2 countries
Study dates
24 Jan 2018to 22 Dec 2026
Phase
Phase 3
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patient must have signed a written informed consent form prior to any study specific procedures
  • Histologically or cytologically confirmed advanced (stage IIIB/IIIC/IV), squamous or non-squamous NSCLC
  • NSCLC patients eligible for treatment with pembrolizumab and chemotherapy according to the European Marketing Authorization:
  • squamous: in combination with carboplatin and either paclitaxel or nab-paclitaxel
  • non squamous with no EGFR or ALK positive mutations: in combination with pemetrexed and a platinum based chemotherapy
  • Patient ≥18 of age
Show all 52Show fewer
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 - 1
  • Life expectancy >3 months
  • Measurable lesion as assessed by RECIST version 1.1
  • Metastases and/or primary tumour eligible for 3 dimensional conventional radiotherapy (3D-CRT) or stereotactic ablative radiotherapy (SABR) in terms of dose constraints at organ at risk (according to QUANTEC review)
  • Patients must have adequate organ function defined by the following laboratory results obtained within 14 days prior to the first study treatment:
  • absolute neutrophil count of ≥1 500 /mm³
  • platelets ≥ 100 000/mm³
  • haemoglobin >9 g/dL (transfusions allowed)
  • creatinine clearance >60 mL/min
  • bilirubin ≤1.5 X upper limit of normal (ULN) (unless Gilbert's syndrome where 3 X ULN is permitted)
  • serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 X ULN (unless documented liver metastasis where ≤5 X ULN is permitted)
  • Alkaline phosphatase (ALP) ≤2.5 X ULN (unless documented bone or liver metastasis where ≤5 X ULN is permitted)
  • International normalized ratio (INR), prothrombin (PT), and prothrombin time (PTT) ≤1.5 X ULN (unless the subject is receiving anticoagulant therapy)
  • Woman of childbearing potential and male patients must agree to use adequate contraception for the duration of study participation and up to 6 months after completing treatment/therapy
  • Patients affiliated to the social security system (or equivalent)
  • Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits, and examinations including follow-up
  • NON-INCLUSION CRITERIA:
  • Non-squamous NSCLC with targetable tumor mutations, activating EGFR mutations or ALK translocation Note: documentation of these mutation for non-squamous histology is mandatory as standard of care
  • Stage IIIB/IIIC NSCLC patient eligible to curative (thoracic radiotherapy or surgery) treatments in first line treatment
  • Prior therapy with T-cell costimulation or checkpoint-targeted agents Note: Stage I-III NSCLC who previously received single-agent anti-PD(L)1 immunotherapy and ultimately develop metastases remain eligible (minimal immunotherapy washout period of 3 months)
  • Clinical need of radiotherapy (e.g.: whole brain irradiation, painful metastasis, bleeding, compressive metastases)
  • Irradiation within 2 months before inclusion
  • Leptomeningeal carcinomatosis, or metastases with indistinct borders making targeting not feasible
  • Patient with evidence of active (presence of symptoms or requiring steroid treatment) central nervous system (CNS) metastases and/or carcinomatous meningitis. Patient with brain metastasis can be included if asymptomatic and not requiring steroids
  • Metastases located within 3 cm of the previously irradiated structures (EQD2doses):
  • Spinal cord previously irradiated to >40 Gy;
  • Brachial plexus previously irradiated to >50 Gy;
  • Small intestine, large intestine, or stomach previously irradiated to >45 Gy;
  • Brainstem previously irradiated to >50 Gy;
  • Lung previously irradiated with prior V20Gy >30%
  • Active autoimmune disease except vitiligo, type-1 diabetes, hypothyroid stabilized with hormonal substitution, psoriasis
  • Symptomatic interstitial lung disease
  • Systemic immunosuppression or systemic immunosuppressive medicinal products within 2 weeks prior to study entry
  • Concomitant treatment with steroids > 10 mg Note1: higher dose of steroids can be prescribed in case of occurrence of toxicities during radiotherapy; prophylactic dose of maximum 1 mg per kg during 2 weeks are authorized during the delivery of more than 6 Gy per fraction Note2: temporary use of steroid (less than 4 weeks) at a dose of 1 mg/kg is accepted
  • Prior invasive malignancy within the past 2 years (except non-melanomatous skin cancer non-invasive carcinoma in-situ of the breast, oral cavity, bladder or cervix)
  • Known Acquired Immune Deficiency Syndrome (AIDS) or severe uncontrolled co-morbidity
  • Known currently active infection including hepatitis B and hepatitis C
  • Patient who was administered a live, attenuated vaccine within 28 days prior to enrolment
  • Patient with any other disease or illness that requires hospitalisation or is incompatible with the study treatment are not eligible. Patient unable to comply with study obligations for geographic, social, or physical reasons, or who is unable to understand the purpose and procedures of the study
  • Patient who have taken any investigational medicinal product or have used an investigational device within 30 days of inclusion
  • Pregnant or breast feeding woman
  • Person deprived of their liberty or under protective custody or guardianship
  • If pemetrexed: patient is unable or unwilling to take folic acid or vitamin B12 supplementation
  • Pre-existing peripheral neuropathy of a severity of grade ≥ 2 by NCI CTCAE v5.0
  • Known hypersensitivity to one of the compounds or substances used in this protocol
  • Major surgery within the 28 days before initiating study treatment

Who cannot join

None listed.

Trial locations and contacts

58 sites in 2 countries.

58 sites in 2 countries

France57 sites

  • Institut de Cancérologie de l'Ouest - Site Paul Papin

    Angers

  • Centre Marie Curie

    Arras

  • Hôpital Privé Arras Les Bonnettes

    Arras

  • Institut Sainte Catherine

    Avignon

  • Centre Pierre Curie

    Beuvry

  • Clinique Ambroise Pare

    Beuvry

  • Hôpital Simone Veil Blois

    Blois

  • Institut Bergonie

    Bordeaux

  • CHRU de Brest

    Brest

  • Centre François Baclesse

    Caen

  • Centre Hospitalier Universitaire De Caen - Hôpital Cote De Nacre

    Caen

  • Centre Hospitalier Dr Jean-Eric TECHER

    Calais

  • Centre hospitalier de Cannes Simone Veil

    Cannes

  • Centre Hospitalier William Morey

    Chalon-sur-Saône

  • Institut de Cancérologie de Bourgogne

    Chalon-sur-Saône

  • Pôle départemental de Cancérologie Libérale 37

    Chambray-lès-Tours

  • Centre Jean Perrin

    Clermont-Ferrand

  • Centre Hospitalier Intercommunal De Creteil

    Créteil

  • Centre Georges Francois Leclerc

    Dijon

  • Institut de Cancérologie de Bourgogne

    Dijon

  • Polyclinique du Parc Drevon

    Dijon

  • Centre André DUTREIX

    Dunkirk

  • Centre Hospitalier de Dunkerque

    Dunkirk

  • Centre de radiothérapie et de cancérologie de Blois

    La Chaussée-Saint-Victor

  • CHU Sud de la Réunion

    La Réunion

  • Hôpital de Bicêtre

    Le Kremlin-Bicêtre

  • Centre Oscar Lambret

    Lille

  • Clinique Chenieux

    Limoges, 87039

  • Hôpital Européen Marseille

    Marseille

  • Hôpital Privé Clairval

    Marseille

  • Centre Hospitalier de Montelimar

    Montélimar

  • Centre de cancérologie du grand Montpellier-Clinique Clementville

    Montpellier

  • Centre Hospitalier des Pays de Morlaix

    Morlaix

  • Centre Azuréen De Cancérologie

    Mougins

  • Hôpital Privé Arnault Tzanck

    Mougins

  • Centre Antoine Lacassagne

    Nice

  • CHU de Nîmes

    Nîmes

  • Fondation Hôpital Saint-Joseph

    Paris

  • Hopital Pitie Salpetriere

    Paris

  • Hopital Tenon

    Paris

  • Centre Catalan d'Oncologie

    Perpignan

  • Institut Jean Godinot

    Reims

  • Centre Frédéric JOLIOT

    Rouen

  • Centre Henri Becquerel

    Rouen

  • Clinique Saint-Hilaire

    Rouen

  • Hopital Charles Nicolle

    Rouen

  • Institut Curie - Hôpital René Huguenin

    Saint-Cloud

  • CHU St Etienne

    Saint-Etienne

  • Centre Joliot Curie

    Saint-Martin-Boulogne

  • Centre Paul Strauss

    Strasbourg

  • Polyclinique de l'Ormeau

    Tarbes

  • CHU de Toulouse Hôpital Larrey

    Toulouse

  • Institut Claudius Regaud

    Toulouse

  • Centre Marie Curie

    Valence

  • Hôpital Privé Drôme Ardèche

    Valence

  • Institut De Cancerologie De Lorraine

    Vandœuvre-lès-Nancy

  • Gustave Roussy

    Villejuif

Other trials in France

Monaco1 site

  • Centre Hospitalier Princesse Grace

    Monaco

Other trials in Monaco

About this study

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").

Read more

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.

Being tested
Radiotherapy, Pembrolizumab, Chemotherapy
Keywords
NSCLC, radiotherapy, immunotherapy, PD(L)-1 blockage
Medical subject headings
Carcinoma, Non-Small-Cell Lung

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • RadiotherapyRadiation

    Also called 3D-CRT or SABR

    Irradiation technique (3D-CRT or SABR) will be at physician discretion.

  • PembrolizumabDrug

    pembrolizumab will be administered as per standard of care every 3 weeks until progression or toxicity

  • ChemotherapyDrug

    Also called Carboplatin, paclitaxel, nab-paclitaxel, cisplatin, pemetrexed

    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

Study groups in NCT03774732
Study groupRoleWhat they receive
Pembrolizumab+ Chemotherapy + RadiotherapyExperimentalIn the experimental arm, patients will receive the same treatment as the control arm (chemotherapy plus pembrolizumab) in addition with conformal 3D radiotherapy (3D-CRT) or stereotactic ablative radiotherapy (SABR) that will be delivered at C2D1, 21 days after the beginning of pembrolizumab using photons/electrons with standard field encompassing tumour. Irradiation technique (3D-CRT or SABR) will be at physician discretion. Ideally, oligometastatic patient (defined by the presence of less than 6 metastases) should be treated with SABR and those with non-oligometastatic disease should be treated with 3D-CRT. Radiotherapy will be delivered a dose of at least 18 Gy in 3 X 6 Gy for 3D-CRT (cf. protocol for possible schemes and volumes restriction). Irradiated tumor size will be ≤5 cm (GTV <65 mL sphere); partial tumor irradiation should be delivered if larger tumor size while respecting dose constraints.
Receives: Radiation: Radiotherapy; Drug: Pembrolizumab; Drug: Chemotherapy
Pembrolizumab+ ChemotherapyActive comparatorSquamous-cell lung carcinoma: Pembrolizumab every 3 weeks and carboplatin + paclitaxel or nab paclitaxel every 3 weeks for 4 cycles then pembrolizumab every 3 or 6 weeks (according to the current version of the SmPC ) Non squamous-cell lung carcinoma: Pembrolizumab every 3 weeks and carboplatin or cisplatin + pemetrexed every 3 weeks for 4 cycles, and then pemetrexed plus pembrolizumab every 3 weeks (according to the current version of the SmPC) Pembrolizumab treatment may be continued as long as patient is experiencing clinical benefit, as assessed by an investigator, in the absence of unacceptable toxicity or symptomatic deterioration attributed to disease progression after an integrated assessment of radiographic data, biopsy results (if available) and clinical status.
Receives: Drug: Pembrolizumab; Drug: Chemotherapy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 1-year Overall Survival

    The primary endpoint of this trial is overall survival (OS) defined as the time from randomization to the date of documented death from any cause or last follow-up.

    Measured: 1 year

Secondary outcomes (7)

  1. Tumour response

    Tumour response is defined as the percentage of patients with a complete response (CR) or partial response (PR), according to RECIST 1.1 and iRECIST (centralized response evaluation).

    Measured: 1 year

  2. Progression-free survival

    Progression-free survival (PFS) is defined as the time from randomization until documented disease progression (PD) according to RECIST 1.1 and iRECIST (centralized response evaluation for both arms), or death, whichever occurs first.

    Measured: 1 year

  3. Local and distant controls in irradiated patients

    Local and distant controls in irradiated patients are defined as the time from randomization to the first documented local event or distant event.

    Measured: 6 months and 1 year

  4. Quality of life of the patients using EORTC-QLQ-C 30

    Quality of life will be assessed using QLQ-C 30 questionnaire from the European Organization for Research and Treatment of Cancer (EORTC). It is a 30-item self-reporting questionnaire developed to assess the quality of life of cancer patients. It is grouped into five functional subscales (role, physical, cognitive, emotional and social functioning). In addition, there are three multi-item symptom scales (fatigue, pain, and nausea and vomiting), individual questions concerning common symptoms in cancer patients,and two questions assessing overall Quality of Life

    Measured: up to 2 years

  5. Acute/Late toxicities

    Acute/ late toxicity will be assessed according to the flowchart and graded by CTCAE v5

    Measured: 1 year

  6. Non-small lung cancer specific survival

    To evaluate, compared to standard of care, whether the addition of radiotherapy improves survival of patients until death from non-small lung cancer

    Measured: 1 year

  7. 2-year Overall survival

    Overall survival (OS) is defined as the time from randomization to the date of documented death from any cause or last follow-up.

    Measured: 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Dec 2018
  2. Study start24 Jan 2018
  3. Primary completion22 Dec 2026 (estimated)
  4. Study completion22 Dec 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
327 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03774732
Sponsor's protocol ID
UC-0107/1718
Acronym
NIRVANA-LUNG
Status last verified
Jan 2026
First submitted
26 Sep 2018
Last updated
25 Feb 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Doyen J, Besse B, Texier M, Bonnet N, Levy A. PD-1 iNhibitor and chemotherapy with concurrent IRradiation at VAried tumor sites in advanced Non-small cell lung cAncer: the Prospective Randomized Phase 3 NIRVANA-Lung Trial. Clin Lung Cancer. 2022 May;23(3):e252-e256. doi: 10.1016/j.cllc.2021.10.008. Epub 2021 Oct 24.

    PubMed 34810130

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Radiotherapy, Pembrolizumab and Chemotherapy in people with Non Small Cell Lung Cancer and Non Small Cell Lung Cancer Metastatic, run by UNICANCER at 58 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 52 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 25 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 58 sites in France, Monaco. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

1-year Overall Survival (time frame: 1 year). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03774732, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Feb 2026.

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NIRVANA-LUNG Clinical Trial NCT03774732 | AzTrials