Oligometastatic Non-small Cell Lung Cancer (NSCLC)Phase 3OliGRAILNCT06840782
First-line Immunotherapy-based Standard of Care and Local Ablative Treatments for Oligometastatic Non-small Cell Lung Cancer Patients.
A Phase 3 study testing Radical local treatment and SoC-based immunotherapy (+/- chemotherapy) in people with Oligometastatic Non-small Cell Lung Cancer (NSCLC), run by Gustave Roussy, Cancer Campus, Grand Paris at 11 sites in France.
Trial summary
First-line immunotherapy-based standard of care and local ablative treatments for oligometastatic non-small cell lung cancer patients: a randomized, multicentre, open-label phase III study Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Oligometastatic Non-small Cell Lung Cancer (NSCLC)
- What is being tested?
- Radical local treatment and SoC-based immunotherapy (+/- chemotherapy)
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 124 participants
- Where
- 11 sitesFrance
- Study dates
- 9 Sep 2025to Feb 2030
- 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
- Histologically proven advanced synchronous oligometastatic stage IV NSCLC.
- NSCLC patients eligible first line immunotherapy-based SoC according to the European Marketing Authorization.
- PDL1 status available.
- Metastases eligible to RLT according to the local multidisciplinary board (MTB): ≤5cm each in CT scan, excluding primary tumour.
- Maximum 5 metastases in 3 organs (EORTC criteria), according to brain MRI and FDG-PET.
- Symptomatic lesions requiring urgent palliative radiation, is permitted prior to randomization. These treated lesions should be counted towards the total number of metastases at the time of enrolment.
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- Clinically required brain metastases (BM) ablation (surgery and/or SBRT) is permitted and BM count within the total number of 5 lesions. The patient would then be randomized to treatment of their extracranial disease.
- Acceptable organ function for RLT.
- ECOG performance status (PS) 0-1.
- Measurable lesions according to RECIST V1.1 on standard imaging.
- Patient aged 18 or more.
- Woman of childbearing potential must agree to use adequate contraception (implant type, vaginal ring, contraceptive pill, contraceptive patch, Intrauterine Device (IUD), etc.) for the duration of study participation and up to 6 months after completing treatment/therapy, in addition, male partners use a condom during this same period. Male patients must agree to use condom for the duration of study participation and up to 6 months after completing treatment/therapy.
- Patients affiliated to the social security system.
- Patient should understand, sign, and date the informed consent form written in French prior to any protocol-specific procedures performed.
- 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.
Who cannot join
- Non-squamous NSCLC with targetable tumour mutations and approved first line targeted therapy (such as EGFR, ALK and ROS1).
- Metastases not eligible to RLT: e.g. brainstem or diffuse serosal metastases (meningeal, pericardial, pleural, peritoneal, mesenteric) or that invades the gastrointestinal tract.
- Brain metastases only, without extra-cerebral metastases.
- Uncontrolled severe comorbidity, symptomatic interstitial lung disease or active infection.
- Prior therapy with T-cell costimulation or immune checkpoint-targeted agents within 1 year.
- Uncontrolled concomitant (<1-year) malignancy except adequately treated basal or squamous cell carcinoma of the skin, or in-situ carcinoma of any organ or in-situ melanoma of the skin.
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- Persons deprived of liberty by judicial or administrative decision.
- Persons subject to a legal protection measure (guardianship, curatorship, safeguard of justice).
- Persons not affiliated to a social security system or equivalent.
Trial locations and contacts
11 sites in 1 country. Contact the study team or a site near you to ask about taking part.
11 sites in 1 country
France11 sites, 11 recruiting
- Recruiting
Centre Sainte-Catherine
Avignon, Provence-Alpes-Côte d'Azur Region, 84000
Nicolas POUREL, MD, +33 (0)4 90 27 60 28, n.pourel@isc84.org
Nicolas POUREL, MD
- Recruiting
Centre François Baclesse
Caen, 14076
Mathieu CESAIRE, 02 31 45 50 50, m.cesaire@baclesse.unicancer.fr
- Recruiting
Institut de Radiothérapie du Sud de l'Oise
Creil, Hauts-de-France, 60100
Andres HUERTAS, MD, +33 (0)3 44 28 41 00, andres.huertas@amethyst.fr
Andres HUERTAS, MD
- Recruiting
Centre Oscar Lambret
Lille, 59000
Florence LE TINIER, 03 20 29 59 59, f-letinier@o-lambret.fr
- Recruiting
Hospices Civils de Lyon (HCL)
Lyon, 69000
Thomas PIERRET, 04 27 85 77 00, thomas.pierret@chu-lyon.fr
- Recruiting
CHU Nice
Nice, 06001
Jacques BOUTROS, 04 92 03 76 09, boutros.j@chu-nice.fr
- Recruiting
Institut de Cancérologie du Gard
Nîmes, 30029
Sylvie VAN HULST, 04 66 68 32 21, sylvie.vanhulst@chu-nimes.fr
- Recruiting
Hôpital Paris Saint- Joseph
Paris, 75014
Charles NALTET, 01 44 12 37 52, cnaltet@ghpsj.fr
- Recruiting
Institut Curie
Saint-Cloud, Île-de-France Region, 92210
Maxime LOO, 01 47 11 16 31, maxime.loo@curie.fr
- Recruiting
Polyclinique Ormeau
Tarbes, 65000
Pierre-Marie PIALAT, 05 62 93 59 29, dr.pialat@grop65.fr
- Recruiting
Gustave Roussy
Villejuif, Île-de-France Region, 94805
Antonin LÉVY, MD, +33 (0)1 42 11 47 57, antonin.levy@gustaveroussy.fr
Antonin LÉVY, MD
About this study
Official title: First-line Immunotherapy-based Standard of Care and Local Ablative Treatments for Oligometastatic Non-small Cell Lung Cancer Patients: a Randomized, Multicentre, Open-label Phase III Study
First-line immunotherapy-based standard of care and local ablative treatments for oligometastatic non-small cell lung cancer patients: a randomized, multicentre, open-label phase III study
- Being tested
- Radical local treatment, SoC-based immunotherapy (+/- chemotherapy)
- Keywords
- Local ablative treatments, First-line immunotherapy, SBRT, Interventional radiology, Minimally invasive surgery
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Radical local treatmentRadiation
Also called SBRT, Interventional radiology, Minimally invasive surgery
RLT of all metastatic sites. The possible RLT options will be SBRT, interventional radiology and/or minimally invasive surgery. Depending on the metastatic site, access and patient condition, the best RLT should be initially discussed in a case-to-case basis at the local multidisciplinary board (MTB).
The primary tumour and initially invaded lymph nodes should be treated during the maintenance phase. Curative-intent approach modalities (e.g. hypofractionated intensity-modulated thoracic radiation therapy or surgery) should be discussed at the local MTB.
SoC-based immunotherapy (+/- chemotherapy)Drug
Current French SoC will be used. Main SoC-based immunotherapy includes:
- Platinum-based chemotherapy combined with an anti PD-1 immunotherapy (pembrolizumab). Pemetrexed-platinum combinations may be used in non- squamous carcinoma, while paclitaxel-platinum combination is favoured in squamous carcinoma.
- Anti PD-1 monotherapy if PD-L1 ≥ 50% is a possible alternative (pembrolizumab or atezolizumab or cemiplimab).
Other alternatives include nivolumab-ipilimumab-chemotherapy or durvalumab-tremelimumab-chemotherapy association. Bevacizumab is not allowed given possible interactions with RLT.
Maintenance/Immunotherapy alone will be pursued at the investigator's discretion according to the standard procedures (toxicity, progression, choice of the patient...).
| Study group | Role | What they receive |
|---|---|---|
| Experimental arm: RLT + SoC-based immunotherapy (+/- chemotherapy) | Experimental | RLT of all metastatic sites should be administered within 3 months after randomization and should not delay SoC-based immunotherapy administration. Receives: Radiation: Radical local treatment; Drug: SoC-based immunotherapy (+/- chemotherapy) |
| Control arm: SoC-based immunotherapy (+/- chemotherapy) | Active comparator | SoC-based immunotherapy (+/- chemotherapy) will be administered every 3 weeks Receives: Drug: SoC-based immunotherapy (+/- chemotherapy) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Survival (OS).
Time from randomization to the date of documented death from any cause or last follow-up.
Measured: From date of randomization up to two years after the randomization of the last patient or documented death.
Secondary outcomes (8)
Progression-free survival (PFS) according to RECIST 1.1.
Time between the randomization date and the date of observation of a progression of the disease according to RECIST 1.1 or death of the patient (all causes combined) or date of last follow-up if the patient is alive without progression or lost to follow up.
Measured: From date of randomization up to two years after the randomization of the last patient or documented death.
immune Progression-free survival (iPFS) according to iRECIST.
Time between the randomization date and the date of observation of an progression of the disease according to iRECIST 1.1 or death of the patient (all causes combined) or date of last follow-up if the patient is alive without progression or lost to follow up.
Measured: From date of randomization up to two years after the randomization of the last patient or documented death.
Number of side effects measured by CTCAE V.5.
Acute/ late adverse events graded by CTCAE v5 (toxic death and serious adverse events) and their imputability to treatment.
Measured: From date of randomization up to two years after the randomization of the last patient or documented death.
EORTC Quality of Life Questionnaire-C30 (EORTC QLQ-C30).
The EORTC Quality of Life Questionnaire-C30 (EORTC QLQ-C30) contains 30 questions and assesses the quality of life of oncological patients multidimensionally over 10 subscales. All sub-scales and the 6 individual items have a score range from 0 to 100 points. A higher score represents better function and a higher quality of life. In the symptom subscale, however, a higher score represents a higher level of symptoms or problems.
Measured: From date of randomization up to 24 months after the last patient included in the study, until the date of first documented progression or date of death from any cause, whichever come first.
EORTC Quality of Life Questionnaire Lung Cancer-specific-13 (QLQ-LC-13).
EORTC Quality of Life Questionnaire Lung Cancer-specific-13 (QLQ-LC-13) is a specific companion module used in conjunction with the EORTC QLQ-C30 and specifically developed for patients with Lung Cancer, and reliable in LC specific Qol assessment. The EORTC QLQ-LC13 comprises 13 item that measure lung cancer-related symptoms. Each items use the same 1-to-4 verbal response scale as the QLQ-C30 items, and domain scores are also transformed to a 0-to-100 metric. A higher score represents better function and a higher quality of life.
Measured: From date of randomization up to 24 months after the last patient included in the study, until the date of first documented progression or date of death from any cause, whichever come first.
EuroQol-5D-5L Questionnaire (EQ-5D-5L).
The EuroQol-5D-5L Questionnaire (EQ-5D-5L) descriptive system of 5 health dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Index scores range from -0.59 to 1; 1 is the best possible health state. Negative values represent health states perceived as worse than dead, which is equal to 0. Used alongside the EQ-5D, the EQ visual analog scale (VAS) is a 20 cm VAS "assessing your own health today" with endpoints labeled "Best imaginable health state" (100) and "Worst imaginable health state" (0).
Measured: From date of randomization up to 24 months after the last patient included in the study, until the date of first documented progression or date of death from any cause, whichever come first.
Clearance of circulating tumour DNA (ctDNA).
ctDNA assessed in plasma.
Measured: At the randomization, then Week 6 and Month 4 after randomization.
Economic evaluation.
Incremental cost per Quality-adjusted life year (QALY based on EQ-5D-5L measures), incremental net monetary benefit. Assess the cost-utility (cost per QALY) of RLT + immunotherapy-based SoC compared to immunotherapy-based SoC alone.
Measured: From date of randomization up to 24 months after the last patient included in the study, until the date of first documented progression or date of death from any cause, whichever come first.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Feb 2025
- Study start9 Sep 2025
- Primary completionFeb 2030 (estimated)
- Study completionFeb 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Oligometastatic Non-small Cell Lung Cancer (NSCLC)Studies of the same condition, open and under way.
- More trials run by Gustave Roussy, Cancer Campus, Grand ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- 124 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Gustave Roussy, Cancer Campus, Grand Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06840782
- Sponsor's protocol ID
- 2023-503326-39-00
- Other IDs
- 2023/3729, 2023
- Acronym
- OliGRAIL
- Status last verified
- Nov 2026
- First submitted
- 16 Jan 2025
- Last updated
- 5 Nov 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- First-line Immunotherapy-based Standard of Care and Local Ablative Treatments for Oligometastatic Non-small Cell Lung Cancer Patients: a Randomized, Multicentre, Open-label Phase III Study
- ClinicalTrials.gov ID
- NCT06840782
- Acronym / sponsor ID
- OliGRAIL / 2023-503326-39-00
- Keywords
- Local ablative treatments, First-line immunotherapy, SBRT, Interventional radiology, Minimally invasive surgery
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 124 participants (estimated)
- Lead sponsor
- Gustave Roussy, Cancer Campus, Grand ParisUniversity, hospital or other
- Study start
- 9 Sep 2025 (actual)
- Primary completion
- Feb 2030 (estimated)
- Study completion
- Feb 2030 (estimated)
- First posted
- 21 Feb 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
First-line immunotherapy-based standard of care and local ablative treatments for oligometastatic non-small cell lung cancer patients: a randomized, multicentre, open-label phase III study
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Experimental arm: RLT + SoC-based immunotherapy (+/- chemotherapy) | Experimental | Radiation: Radical local treatment, Drug: SoC-based immunotherapy (+/- chemotherapy)RLT of all metastatic sites should be administered within 3 months after randomization and should not delay SoC-based immunotherapy administration. |
| Control arm: SoC-based immunotherapy (+/- chemotherapy) | Active comparator | Drug: SoC-based immunotherapy (+/- chemotherapy)SoC-based immunotherapy (+/- chemotherapy) will be administered every 3 weeks |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Histologically proven advanced synchronous oligometastatic stage IV NSCLC.
- NSCLC patients eligible first line immunotherapy-based SoC according to the European Marketing Authorization.
- PDL1 status available.
- Metastases eligible to RLT according to the local multidisciplinary board (MTB): ≤5cm each in CT scan, excluding primary tumour.
- Maximum 5 metastases in 3 organs (EORTC criteria), according to brain MRI and FDG-PET.
Key exclusion criteria (9 listed)
- Non-squamous NSCLC with targetable tumour mutations and approved first line targeted therapy (such as EGFR, ALK and ROS1).
- Metastases not eligible to RLT: e.g. brainstem or diffuse serosal metastases (meningeal, pericardial, pleural, peritoneal, mesenteric) or that invades the gastrointestinal tract.
- Brain metastases only, without extra-cerebral metastases.
- Uncontrolled severe comorbidity, symptomatic interstitial lung disease or active infection.
- Prior therapy with T-cell costimulation or immune checkpoint-targeted agents within 1 year.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Radical local treatmentAlso: SBRT, Interventional radiology, Minimally invasive surgeryRLT of all metastatic sites. The possible RLT options will be SBRT, interventional radiology and/or minimally invasive surgery. Depending on the metastatic site, access and patient condition, the best RLT should be initially discussed in a case-to-case basis at the local multidisciplinary board (MTB). The primary tumour and initially invaded lymph nodes should be treated during the maintenance phase. Curative-intent approach modalities (e.g. hypofractionated intensity-modulated thoracic radiation therapy or surgery) should be discussed at the local MTB. | Radiation | Experimental arm: RLT + SoC-based immunotherapy (+/- chemotherapy) |
| SoC-based immunotherapy (+/- chemotherapy)Current French SoC will be used. Main SoC-based immunotherapy includes: * Platinum-based chemotherapy combined with an anti PD-1 immunotherapy (pembrolizumab). Pemetrexed-platinum combinations may be used in non- squamous carcinoma, while paclitaxel-platinum combination is favoured in squamous carcinoma. * Anti PD-1 monotherapy if PD-L1 ≥ 50% is a possible alternative (pembrolizumab or atezolizumab or cemiplimab). Other alternatives include nivolumab-ipilimumab-chemotherapy or durvalumab-tremelimumab-chemotherapy association. Bevacizumab is not allowed given possible interactions with RLT. Maintenance/Immunotherapy alone will be pursued at the investigator's discretion according to the standard procedures (toxicity, progression, choice of the patient...). | Drug | Control arm: SoC-based immunotherapy (+/- chemotherapy), Experimental arm: RLT + SoC-based immunotherapy (+/- chemotherapy) |
Primary outcome
Overall Survival (OS).
Time frame: From date of randomization up to two years after the randomization of the last patient or documented death.
Time from randomization to the date of documented death from any cause or last follow-up.
8 secondary outcomes
Progression-free survival (PFS) according to RECIST 1.1.
Time frame: From date of randomization up to two years after the randomization of the last patient or documented death.
immune Progression-free survival (iPFS) according to iRECIST.
Time frame: From date of randomization up to two years after the randomization of the last patient or documented death.
Number of side effects measured by CTCAE V.5.
Time frame: From date of randomization up to two years after the randomization of the last patient or documented death.
EORTC Quality of Life Questionnaire-C30 (EORTC QLQ-C30).
Time frame: From date of randomization up to 24 months after the last patient included in the study, until the date of first documented progression or date of death from any cause, whichever come first.
EORTC Quality of Life Questionnaire Lung Cancer-specific-13 (QLQ-LC-13).
Time frame: From date of randomization up to 24 months after the last patient included in the study, until the date of first documented progression or date of death from any cause, whichever come first.
EuroQol-5D-5L Questionnaire (EQ-5D-5L).
Time frame: From date of randomization up to 24 months after the last patient included in the study, until the date of first documented progression or date of death from any cause, whichever come first.
Clearance of circulating tumour DNA (ctDNA).
Time frame: At the randomization, then Week 6 and Month 4 after randomization.
Economic evaluation.
Time frame: From date of randomization up to 24 months after the last patient included in the study, until the date of first documented progression or date of death from any cause, whichever come first.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Nov 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
11 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Radical local treatment and SoC-based immunotherapy (+/- chemotherapy) in people with Oligometastatic Non-small Cell Lung Cancer (NSCLC), run by Gustave Roussy, Cancer Campus, Grand Paris at 11 sites in France.
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 15 inclusion and 9 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: looking for participants now, as of the sponsor's last update on 5 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in France. 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?
Contact Antonin LEVY (01 42 11 47 57, antonin.levy@gustaveroussy.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Survival (OS). (time frame: From date of randomization up to two years after the randomization of the last patient or documented death.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 5 Nov 2026.