Upon signature of the informed consent and verification of the screening results, eligible participants will be randomized between two therapeutic strategies:~Arm A (experimental arm): cryoablation of visceral lesion or bone metastasis excluding liver and sclerotic bone metastases combined with pembrolizumab and pemetrexed-carboplatin prescribed as per market authorization.~Arm B (standard arm): pembrolizumab and pemetrexed-carboplatin prescribed as per market authorization.~Pembrolizumab treatment should begin no later than 7 days after randomization. The cryoablation treatment should be performed within 6 weeks after the first administration of pembrolizumab.~RECIST v1.1 tumour assessment:Tumour response will be defined and assessed as per the Response Evaluation Criteria in Solid Tumors (RECIST v1.1).~A comprehensive workup will be performed at baseline and every 9 weeks.~The same method will be used to evaluate each identified lesion both at baseline and throughout the study.~Treatment will be administered as long as no disease progression or unacceptable toxicity is found, or as long as no other reasons for treatment discontinuation are met.~Assessment of efficacy will be essentially based on a set of measurable lesions identified at baseline as target lesions and followed until disease progression and following the RECIST v1.1 criteria.~Confirmation of response at least 4 weeks later is not required in this randomized study where response is not the primary endpoint.~SAFETY :Patients will be evaluable for safety if they have received at least one treatment administration. Safety profile will be continuously followed during treatment up to 90 days after the last immunotherapy treatment administration or until the start of a new antitumor therapy or until 12 months of treatment, whichever occurs first.~STUDY PROCEDURES :~Blood sample will be collected at baseline (Day 1: before treatment initiation), Day 1 cycle 2 (Day 21 +/- 3 days), Day 1 cycle 3 (Day 42 +/- 3 days) and progression.~Patients will be asked to provide samples of biopsy tissue at screening (prior to anticancer agent with immunomodulatory activity treatment initiation), during treatment (day 42 +/- 3 days) and at disease progression as follows.~Only for consented patient (optional), stool sample will be collected at baseline (Day 1: before treatment initiation).~All randomized patients will be followed up until death or the end of the follow-up period, defined as 36 months after randomization, whichever occurs first. For all patients, treatments regimen, tumor response during and/or after treatment, survival follow-up will be collected on study database:~Every 3 months until loco-regional relapse or metastasis evidence, death or until the date of study termination, whichever occurs first,~Every 6 months after loco-regional relapse or metastasis evidence, until death or until the date of study termination, whichever occurs first.
This study aims to compare the one-year survival benefit of the association of cryoablation-pembrolizumab-pemetrexed-carboplatin versus pembrolizumab-pemetrexed-carboplatin in metastatic lung adenocarcinoma patients.~This is a multicenter, prospective, open-labeled, 2-arm comparative randomized (1:1) phase III trial.~Patients will be randomized with a 1:1 ratio into:~Arm A (experimental arm): cryoablation of one visceral lesion or bone metastasis excluding liver and sclerotic bone metastases combined with pembrolizumab and pemetrexed-carboplatin prescribed as per market authorization.~Arm B (standard arm): pembrolizumab and pemetrexed-carboplatin prescribed as per market authorization.~Pembrolizumab and pemetrexed-carboplatin will be prescribed and administered at the dose recommended by market authorization.~Cryoablation treatment should be performed within 6 weeks after the first administration of pembrolizumab. No treatment switching permitted.