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

NCT ID: NCT06840782

Last Updated: 2025-09-15

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 124 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-09-09
• Study Completion Date: 2030-02-28

Brief 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

Conditions

Oligometastatic Non-small Cell Lung Cancer (NSCLC)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Radical local treatment

Intervention Type: RADIATION

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)

Intervention Type: 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...).

Control arm: SoC-based immunotherapy (+/- chemotherapy)

SoC-based immunotherapy (+/- chemotherapy) will be administered every 3 weeks

Group Type: ACTIVE_COMPARATOR

SoC-based immunotherapy (+/- chemotherapy)

Intervention Type: 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...).

Interventions

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.

Intervention Type: RADIATION

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...).

Intervention Type: DRUG

Other Intervention Names

SBRT; Interventional radiology; Minimally invasive surgery

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Gustave Roussy, Cancer Campus, Grand Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Institut de Radiothérapie du Sud de l'Oise

Creil, Hauts-de-France, France

Site Status: RECRUITING

Centre Sainte-Catherine

Avignon, Provence-Alpes-Côte d'Azur Region, France

Site Status: RECRUITING

Gustave Roussy

Villejuif, Île-de-France Region, France

Site Status: RECRUITING

Countries

France

Central Contacts

Antonin LÉVY, MD

Role: CONTACT

antonin.levy@gustaveroussy.fr

+33 (0)1 42 11 47 57

Facility Contacts

Andres HUERTAS, MD

Role: primary

andres.huertas@amethyst.fr

+33 (0)3 44 28 41 00

Nicolas POUREL, MD

Role: primary

n.pourel@isc84.org

+33 (0)4 90 27 60 28

Antonin LÉVY, MD

Role: primary

antonin.levy@gustaveroussy.fr

+33 (0)1 42 11 47 57

Other Identifiers

2023/3729

Identifier Type: OTHER

Identifier Source: secondary_id

2023-503326-39-00

Identifier Type: -

Identifier Source: org_study_id