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 (OliGRAIL)

Prior treatment

• 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.

Other illness

• Uncontrolled severe comorbidity, including but not limited to symptomatic interstitial lung disease or active infection.

Lab values

• Non-squamous NSCLC with targetable tumour mutations and approved first line targeted therapy (such as EGFR, ALK and ROS1).

Other

• Metastases not eligible to RLT: e.g. brainstem or diffuse serosal metastases (meningeal, pericardial, pleural, peritoneal, mesenteric) or that invades the gastrointestinal tract.

• Histologically proven advanced oligometastatic stage IV NSCLC.
• 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 remaining disease
• Acceptable organ function for RLT
• ECOG performance status (PS) 0-1.
• Measurable lesions according to RECIST V1.1 or evaluable disease on standard imaging,
• Patient should understand, sign, and date the informed consent form written in French prior to any protocol-specific procedures performed.
• 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.
• 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.
• Aga > 18 years
• NSCLC patients eligible first line immunotherapy-based SoC according to the European Marketing Authorization. PDL1 status available.
• Metastases eligible to RLT(minimally invasive surgery, SBRT and/or interventional radiology) 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