The use of neoadjuvant immuno-chemotherapy could improve survival outcomes of patients eligible for sequential radio-chemotherapy comparing to the benefit already obtained with maintenance immunotherapy.

Inclusion Criteria:

1. Patients must have signed and dated an IRB/IEC approved written informed consent form in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol related procedures that are not part of normal subject care.

2. Patients must be willing and able to comply with scheduled visits, treatment schedule, and laboratory testing.

3. Age ≥ 18 years.

4. Histologically or cytologically confirmed locally advanced non small cell lung cancer (NSCLC) stage IIIA non resectable, IIIB or IIIC accordingly to 8th classification TNM, UICC 2015.

5. Patients over 70 years of age with Eastern Cooperative Oncology Group Performance Status (ECOG PS) PS of 0 to 1.

   Or Patients under 70 years of age with ECOG PS of 0 to 1 and a score ≥ 3 according to the Charlson comorbidity criterion or ECOG PS 2.

6. Patients eligible for treatment with sequential radio-chemotherapy validated by multidisciplinary committee.

7. Measurable disease according to RECIST 1.1.

8. Respiratory function:

   • FEV1 ≥ 40% of theoretical value,
   • DLCO ≥ 40%.

9. Bone marrow function:

   • absolute neutrophil count (ANC) ≥ 1.5.109/L,
   • platelets ≥ 100.109/L,
   • hemoglobin ≥ 9 g/dl.

10. Renal and hepatic function:

    • estimated creatinine clearance ≥ 45 ml/min,
    • bilirubin ≤1.5xULN,
    • AST ALT ≤3xULN,
    • Albumin ≥28g/dl.

11. Participant has national health insurance coverage.

12. Effective method of contraception during the treatment and during the 6 months following the last dose for patients of childbearing potential and for male subjects who are sexually active with a woman of childbearing potential.

Exclusion Criteria:

1. Immunotherapy or chemotherapy contra-indicated.
2. Patients eligible for treatment with concomitant radio-chemotherapy validated by multidisciplinary committee.
3. Stage I or II NSCLC.
4. Previously received a treatment with anti-PD1/PDL1, anti-CTLA, or other antineoplastic immunotherapy or chemotherapy for NSCLC.
5. Histology other than primary non-small cell lung cancer.
6. Patients with an activating EGFR mutation or ALK or ROS1 translocation.
7. Metastatic NSCLC including brain metastasis.
8. Patients not eligible for curative radiotherapy (tumor extension, predictable dose constraints that cannot be met).
9. Severe uncontrolled comorbidities or severe intercurrent disease: acute coronary syndrome less than 3 months old, unstable angina, heart failure with LVEF ≤30%, uncontrolled hypertension, Child B or C cirrhosis, severe sepsis, myocarditis or any other active conditions that would contraindicate chemotherapy, immunotherapy, or radiotherapy in the opinion of the investigator.
10. Weight loss ≥15% of total body weight in the last 6 months.
11. ECOG PS upper 2
12. Active autoimmune pathology. History of autoimmune pathology including myasthenia, Guillain-Barre syndrome, lupus erythematosus, antiphospholipid syndrome, Wegener's granulomatosis, glomerulonephritis, inflammatory bowel disease, vasculitis, sarcoidosis, uveitis. Autoimmune thyroid pathologies under replacement therapy as well as type 1 diabetes under insulin are authorized.
13. History of idiopathic pulmonary fibrosis, organized pneumopathy or signs of active interstitial pulmonary pathology on CT scan.
14. Any immunosuppressive therapy received within 28 days and corticosteroids > 10mg/day of prednisone or equivalent received within 7 days prior the start of chemotherapy excepted hydrocortisone replacement for adrenal insufficiency or pituitary disease not considered immunosuppressive therapy.
15. Chronic active infection including tuberculosis, HIV, hepatitis B (HBsAg positive) or C. Patients with a history of cured hepatitis B (anti HBc and absence of negative HBs antigen) are eligible. In case of hepatitis C (anti HCV Ac) patients are eligible if the HCV PCR is negative.
16. Severe infections (including covid-19 infection) within 4 weeks prior to initiation of study treatment, including but not limited to hospitalization for complications of infection, bacteraemia, or severe pneumonia.
17. History of neoplastic disease less than 3 years old or progressive (except basal cell carcinoma of the skin and carcinoma in situ of the uterus).
18. History of thoracic radiotherapy.
19. Live attenuated vaccine received within 28 days of starting chemotherapy
20. History of organ or bone marrow transplantation.
21. Major surgery within 4 weeks of starting treatment.
22. Patient already included in another therapeutic trial.
23. Positive pregnancy test or breastfeeding woman.
24. Protected adults (under guardianship or curatorship).
25. Inability to undergo medical monitoring of the study (for geographical, social and/or physical reasons).
26. Patients unable to understand the study.