Adjuvant Chemotherapy +/- Cemiplimab and Sequential Hypofractionated Radiotherapy in Unfit or Elderly Patients With Stage III Lung Cancer

Inclusion Criteria:

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

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

3. Age ≥ 18 years.

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

5. Patients over 70 years of age with Eastern Cooperative Oncology Group PerformanceStatus (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 accordingto the Charlson comorbidity criterion or ECOG PS 2.

6. Patients eligible for treatment with sequential radio-chemotherapy validated bymultidisciplinary 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 monthsfollowing the last dose for patients of childbearing potential and for male subjectswho 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 bymultidisciplinary committee.

3. Stage I or II NSCLC.

4. Previously received a treatment with anti-PD1/PDL1, anti-CTLA, or otherantineoplastic 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 doseconstraints that cannot be met).

9. Severe uncontrolled comorbidities or severe intercurrent disease: acute coronarysyndrome less than 3 months old, unstable angina, heart failure with LVEF ≤30%,uncontrolled hypertension, Child B or C cirrhosis, severe sepsis, myocarditis or anyother active conditions that would contraindicate chemotherapy, immunotherapy, orradiotherapy 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'sgranulomatosis, glomerulonephritis, inflammatory bowel disease, vasculitis,sarcoidosis, uveitis. Autoimmune thyroid pathologies under replacement therapy aswell as type 1 diabetes under insulin are authorized.

13. History of idiopathic pulmonary fibrosis, organized pneumopathy or signs of activeinterstitial pulmonary pathology on CT scan.

14. Any immunosuppressive therapy received within 28 days and corticosteroids > 10mg/dayof prednisone or equivalent received within 7 days prior the start of chemotherapyexcepted hydrocortisone replacement for adrenal insufficiency or pituitary diseasenot 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 negativeHBs antigen) are eligible. In case of hepatitis C (anti HCV Ac) patients areeligible if the HCV PCR is negative.

16. Severe infections (including covid-19 infection) within 4 weeks prior to initiationof study treatment, including but not limited to hospitalization for complicationsof infection, bacteraemia, or severe pneumonia.

17. History of neoplastic disease less than 3 years old or progressive (except basalcell 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, socialand/or physical reasons).

26. Patients unable to understand the study.