Durvalumab Maintenance After Thoracic Chemoradiotherapy in Frail Small Cell Lung Cancer Patients Whose Disease is Limited to the Thorax

Inclusion Criteria: Criteria for Screening

1. Patient must have signed a first written informed consent form prior to screeningvisit and to any trial specific procedures.
2. Histological confirmation of SCLC.
3. Limited disease (T0-T4, N0-N3 and M0) according to the TNM classification 8th editionor to the VALSG 2-stage classification. As per standard guidelines a completeradiological evaluation has to be performed within 28 days before the start ofinduction chemotherapy including all the radiological exams below:

• Total body PET- scan.
• Contrast enhanced CT-scan of thorax and upper abdomen.
• Contrast enhanced MRI or CT-scan of brain.

4. Measurable disease according to RECIST v1.1 criteria.
5. Patients must not have been previously treated for the SCLC. Note: patients who havealready begun the initial CRT are eligible.
6. Patients ≥18 years old.
7. Body weight >30 kg.
8. Patients can be candidate to concomitant or sequential thoracic CRT by IMRT. Patientshave to receive at least 60 Gy (one-daily fraction of 1.8-2 Gy) or 45 Gy twice daily (1.5 Gy per fraction) combined with cisplatin-etoposide regimen or with carboplatinAUC5 to AUC6 etoposide regimen.
9. Patients that received previous thorax radiotherapy may be eligible if they canreceive the CRT schedule planned in the clinical study according to previousirradiation fields and, in any case, after the medical monitor agreement.
10. Women of childbearing potential must have a negative serum beta-HCG test before thebeginning of the trial, during the study treatment and for a period of at least 3months after the last administration of the experimental drug.
11. All sexually active men and women of childbearing potential must use an effectivecontraception method for the duration of study treatment and for 3 months aftercompleting treatment.
12. Patients affiliated to the social security system.
13. Patient must be willing and able to comply with the protocol for the duration of thetrial including undergoing treatment and scheduled visits, and examinations includingfollow-up. Criteria for Randomization:
14. Patient must have signed a second written informed consent form prior to randomizationand to any specific trial procedure.
15. Patients must have completed concomitant or sequential thoracic CRT by IMRT: Patients that received concomitant or sequential thoracic CRT must have received atleast 60 Gy (one-daily fraction of 1.8-2 Gy) or 45 Gy twice daily (1.5 Gy perfraction) combined with cisplatin-etoposide regimen or with carboplatin AUC5 to AUC6etoposide regimen.
16. Confirmation of disease control (SD, CR or PR) at radiological assessment withcontrast enhanced thorax and upper abdomen CT-scan or PET-CT and contrast enhancedbrain CT-scan or MRI after the thoracic CRT according to RECIST v1.1.
17. Use of brain MRI in case of PCI avoidance is mandatory. PCI has to be prescribedaccording to the investigator's choice and the local recommendations.
18. Patients must belong to one of these groups at the screening visit after the thoracicCRT :

• ECOG PS 2.
• ECOG PS 0-1 and older than 70.
• ECOG PS 0-1 and who did not receive a concomitant thoracic CRT because ofcomorbidities (radiotherapy beginning before D1C3 of chemotherapy).

6. Adequate haematological function

• Haemoglobin >9 g/dL.
• Platelet count >100 x 10⁹L.
• Neutrophil count >1.5 x 10⁹L.

7. Adequate renal function with a creatinine clearance ≥40 ml/min calculated with theCockcroft-Gault formula.
8. Adequate hepatic function:

• Total bilirubin <1.5 Upper limit of normal (ULN).
• AST and ALT <2.5 ULN.
• Alkaline phosphatase <2.5 ULN.

9. HRQoL questionnaire performed.
10. Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy with theexception of alopecia, vitiligo, and the laboratory values defined in the inclusioncriteria.

Exclusion Criteria:

1. History of another primary malignancy except for
2. Malignancy treated with curative intent and with no known active disease ≥5 yearsbefore the first dose of durvalumab and of low potential risk for recurrence.
3. Adequately treated non-melanoma skin cancer or lentigo maligna without evidenceof disease.
4. Adequately treated carcinoma in situ without evidence of disease.
5. Uncontrolled intercurrent illness, including but not limited to, ongoing or activeinfection, symptomatic congestive heart failure, uncontrolled hypertension, unstableangina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronicgastrointestinal conditions associated with diarrhea, or psychiatric illness thatwould limit compliance with study requirement, substantially increase risk ofincurring AEs or compromise the ability of the patient to give written informedconsent.
6. Active or prior documented autoimmune or inflammatory disorders (includinginflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [withthe exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome,or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoidarthritis, hypophysitis, uveitis, etc]). The following are exceptions to thiscriterion:
7. Patients with vitiligo or alopecia
8. Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable onhormone replacement
9. Any chronic skin condition that does not require systemic therapy
10. Patients without active disease in the last 5 years may be included but onlyafter consultation with the study physician
11. Patients with celiac disease controlled by diet alone.
12. Any concurrent chemotherapy, immune checkpoint inhibitors, biologic, or hormonaltherapy for cancer treatment. Concurrent use of hormonal therapy fornon-cancer-related conditions (e.g., hormone replacement therapy) is acceptable.
13. History of leptomeningeal carcinomatosis.
14. Major surgical procedure (as defined by the Investigator) including surgical resectionof the primary disease, within 28 days prior to the first dose of IMP. Note: Localsurgery of isolated lesions for palliative intent is acceptable.
15. History of allogenic organ transplantation.
16. History of active primary immunodeficiency.
17. Known active infection including tuberculosis (clinical evaluation that includesclinical history, physical examination and radiographic findings, or TB testing inline with local practice) and hepatitis B and hepatitis C (positive hepatitis C virus [HCV] antibody, hepatitis B virus [HBV] surface antigen [HBsAg] or HBV core antibody [anti-HBc]).Patients with a past or resolved HBV infection (defined as the presence ofhepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Patientspositive for HCV antibody are eligible only if polymerase chain reaction is negativefor HCV RNA. Patients known to have been tested positive for human immunodeficiencyvirus (HIV) (positive HIV 1/2 antibodies) are not eligible.
18. Current or prior use of immunosuppressive medication within 14 days before the firstdose of durvalumab. The following are exceptions to this criterion:
19. Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intraarticular injection).
20. Systemic corticosteroids at physiologic doses not to exceed 10 mg/day ofprednisone or its equivalent.
21. Steroids as premedication for hypersensitivity reactions (e.g., CT-scanpremedication).
22. Receipt of live attenuated vaccine within 30 days prior to the first dose ofdurvalumab. Note: Patients randomized in experimental arm should not receive live vaccine whilstreceiving durvalumab and up to 30 days after the last dose of durvalumab.
23. Patients with known or suspected hypersensitivity to durvalumab or any of itsexcipients.
24. Patients who participated in another therapeutic trial within the 30 days prior to thestart of the trial (screening phase included).
25. Prior randomisation or treatment in a previous durvalumab clinical study regardless oftreatment arm assignment.
26. Female patients who are pregnant or breast feeding or male or female patients ofreproductive potential who are not willing to employ effective birth control fromscreening to 90 days after the last dose of durvalumab monotherapy.
27. Presence of any psychological, familial, sociological or geographical conditionpotentially hampering compliance with the study protocol and follow-up schedule.
28. Persons deprived of their liberty or under protective custody or guardianship.