First-line Immunotherapy-based Standard of Care and Local Ablative Treatments for Oligometastatic Non-small Cell Lung Cancer Patients. (OliGRAIL)

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

Study Overview

• Status: Recruiting
• Conditions: Oligometastatic Non-small Cell Lung Cancer (NSCLC)
• Intervention / Treatment: Radiation: Radical local treatment; Drug: SoC-based immunotherapy (+/- chemotherapy)

• Study Type: Interventional
• Enrollment (Estimated): 124
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Antonin LÉVY, MD; Phone Number: +33 (0)1 42 11 47 57; Email: antonin.levy@gustaveroussy.fr

Study Locations

• France
  • Hauts-de-France
    • Creil, Hauts-de-France, France, 60100
      • Recruiting
      • Institut de Radiothérapie du Sud de l'Oise
      • Contact: Andres HUERTAS, MD; Phone Number: +33 (0)3 44 28 41 00; Email: andres.huertas@amethyst.fr
      • Principal Investigator: Andres HUERTAS, MD
  • Provence-Alpes-Côte d'Azur Region
    • Avignon, Provence-Alpes-Côte d'Azur Region, France, 84000
      • Recruiting
      • Centre Sainte-Catherine
      • Contact: Nicolas POUREL, MD; Phone Number: +33 (0)4 90 27 60 28; Email: n.pourel@isc84.org
      • Principal Investigator: Nicolas POUREL, MD
  • Île-de-France Region
    • Villejuif, Île-de-France Region, France, 94805
      • Recruiting
      • Gustave Roussy
      • Principal Investigator: Antonin LÉVY, MD
      • Contact: Antonin LÉVY, MD; Phone Number: +33 (0)1 42 11 47 57; Email: antonin.levy@gustaveroussy.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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.
• 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.

Exclusion Criteria:

• 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.
• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental arm: RLT + 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.	Radiation: Radical local treatment; 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.; Other Names: SBRT; Interventional radiology; Minimally invasive surgery; Drug: 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...).
Active Comparator: Control arm: SoC-based immunotherapy (+/- chemotherapy); SoC-based immunotherapy (+/- chemotherapy) will be administered every 3 weeks	Drug: 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...).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS).	Time from randomization to the date of documented death from any cause or last follow-up.	From date of randomization up to two years after the randomization of the last patient or documented death.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	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.	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.	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).	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.	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.	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.

Collaborators and Investigators

• Sponsor: Gustave Roussy, Cancer Campus, Grand Paris

Study record dates

Study Major Dates

• Study Start (Actual): September 9, 2025
• Primary Completion (Estimated): February 1, 2030
• Study Completion (Estimated): February 1, 2030

Study Registration Dates

• First Submitted: January 16, 2025
• First Submitted That Met QC Criteria: February 18, 2025
• First Posted (Actual): February 21, 2025

Study Record Updates

• Last Update Posted (Estimated): September 15, 2025
• Last Update Submitted That Met QC Criteria: September 12, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: SBRT; Minimally invasive surgery; Interventional radiology; Local ablative treatments; First-line immunotherapy
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Therapeutics; Surgical Procedures, Operative; Minimally Invasive Surgical Procedures; Drug Therapy
• Other Study ID Numbers: 2023-503326-39-00; 2023/3729 (Other Identifier: CSET number (Gustave Roussy ID))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No