Cryoablation in Combination (or Not) With Pembrolizumab and Pemetrexed-carboplatin in 1st-line Treatment for Patients With Metastatic Lung Adenocarcinoma

Inclusion Criteria:

1. Histologically or cytologically confirmed non-small lung adenocarcinoma.
2. Metastatic disease.
3. Treatment with pembrolizumab in combination with pemetrexed-carboplatin as per market authorization.
4. At least two target lesions (RECIST1.1), measurable with CT or MRI :

   1. One target lesion that is amenable for accurate repeated measurements,
   2. One target lesion (15-40 mm) that is amenable for cryoablation treatment including lung, kidney, adrenal, soft tissue and lytic bone lesions. Liver and sclerotic bone lesions are not allowed to be treated by cryoablation.
5. Age ≥ 18.
6. Performance status ≤ 2.
7. Women of childbearing potential must have a negative serum pregnancy test prior to registration.
8. Recovery to grade ≤ 1 from any adverse event derived from previous treatment (excluding alopecia)
9. Patients with a social security in compliance with the French law (Loi Jardé).
10. Patients must be willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures.
11. Voluntarily signed and dated written informed consents prior to any study specific procedure.

Exclusion Criteria:

1. Squamous cell tumors and other than adenocarcinoma.
2. Prior systemic treatment for advanced non-small cell lung cancer (except adjuvant therapy after complete resection).
3. Current or prior use of immunosuppressive medication including any use of oral glucocorticoids, within 21 days before the first dose of pembrolizumab.
4. Known contra-indication and/or hypersensitivity to PD1/PD-L1 antagonist and/or cytotoxic therapy.
5. Known contra-indication to cryoablation.
6. Abnormal coagulation contraindicating biopsy.
7. Prior or concurrent malignant disease diagnosed or treated in the last 2 years except for adequately treated in situ carcinoma of the cervix, basal or squamous skin cell carcinoma or incidentally discovered good prognosis prostate cancer (T stage \< pT3 and Gleason ≤ 7).
8. Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy.
9. Subjects who participated in an investigational drug or device study within 28 days prior to study entry.
10. Known infection with HIV, hepatitis B, or hepatitis C.
11. Females who are pregnant or breast-feeding.
12. Men or women refusing contraception.
13. Concomitant disease or condition that could interfere with the conduct of the study, or that would, in the opinion of the investigator, pose an unacceptable risk to the subject in this study.
14. Previous enrolment in the present study.
15. Individuals deprived of liberty or placed under legal guardianship.