Phase-II Trial of Induction Chemotherapy and Chemoradiotherapy Plus/Minus Durvalumab and Consolidation Immunotherapy in Patients With Resectable Stage III NSCLC.

Inclusion Criteria:

1. Body weight >30 kg
2. Age ≥ 18 years and < 75 years
3. Male or female patients. Female (as well as male) patients have to take care ofeffective measures of anticonception
4. Histologically proven non-small cell lung cancer
5. Selected patients with non-small cell lung cancer stages IIIA and IIIB:
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
7. Resectable disease at the time of inclusion
8. Fulfillment of adequate criteria for functional and medical resectability as describedin the European Respiratory Society (ERS)/European Society of Thoracic Surgeons (ESTS)guidelines [Brunelli et al 2009] and acceptable general clinical condition formultimodality treatment (interdisciplinary committee)
9. Capable of giving signed informed consent which includes compliance with therequirements and restrictions listed in the informed consent form (ICF) and in thisprotocol. Written informed consent and any locally required authorization (e.g,European Union [EU] Data Privacy Directive in the EU) obtained from the patient/legalrepresentative prior to performing any protocol-related procedures, includingscreening evaluations.
10. Must have a life expectancy of > 12 weeks
11. Adequate normal organ and marrow function
12. Evidence of post-menopausal status or negative urinary or serum pregnancy test forfemale pre-menopausal patients. Women will be considered post-menopausal if they havebeen amenorrheic for 12 months without an alternative medical cause. The followingage-specific requirements apply:
13. Patient is willing and able to comply with the protocol for the duration of the studyincluding undergoing treatment and scheduled visits and examinations including followup.
14. Stable cardiac function (no Myocardial infarction (MI) within 6 months, no heartfailure according to New York Heart Association (NYHA) III-IV).

Exclusion Criteria:

1. resectable IIB or selected IIIA (T3N0; T3N1)
2. unresectable disease pre-treatment
3. mixed histology with areas of small cell carcinoma (neuroendocrine markers)
4. clinically symptomatic vena cava superior syndrome
5. diffuse mediastinal involvement
6. patients with T3N3 and T4N3 tumors (IIIC according to International Association forthe Study of Lung Cancer (IASLC)/Union Internationale Contre le Cancer (UICC) 8)
7. invasion of the thoracic aorta (T4 - aorta)
8. invasion of the heart (except left atrium - T4 - heart)
9. invasion of the esophagus (T4 - esophagus)
10. invasion of spine (T4 - spine)
11. (full blown) Pancoast-syndrome in tumors of the superior sulcus (T3-4 Nx)
12. malignant (positive) pericardial effusion (M1a - pericardial effusion)
13. malignant (positive) pleural effusion (M1a - pleural effusion)
14. involvement of the contralateral hilar nodes (if any data available)
15. endobronchial tumor extension to the contralateral main stem bronchus
16. ipsi- or contralateral supraclavicular nodes (N3 - supraclavicular nodes)
17. lung or heart function not allowing at the time of inclusion the intended surgicalprocedure
18. previous administration of chemotherapy and/or radiotherapy
19. previous immunotherapy
20. insufficient patients compliance (e.g. symptomatic psychiatric disorder)
21. loss of weight > 10 % in the last six months
22. missing written informed consent or definitive refusal for participation
23. Participation in another clinical study with an investigational product during thelast 12 months
24. Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of aninterventional study
25. Must not have required the use of additional immunosuppression other thancorticosteroids for the management of an Adverse Event (AE), not have experiencedrecurrence of an AE if re-challenged, and not currently require maintenance doses of > 10 mg prednisone or equivalent per day
26. History of idiopathic pulmonary fibrosis, pneumonitis (including drug induced),organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizingpneumonia, etc.), or evidence of active pneumonitis on screening chest CT scan
27. Any concurrent chemotherapy, Intraperitoneal (IP), biologic, or hormonal therapy forcancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable.
28. Major surgical procedure (as defined by the Investigator) within 28 days prior to thefirst dose of IP. Note: Local surgery of isolated lesions for palliative intent isacceptable.
29. History of allogenic organ transplantation.
30. History of a stem cell transplantation
31. 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.]).
32. 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/socialsituations that would limit compliance with study requirement, substantially increaserisk of incurring AEs or compromise the ability of the patient to give writteninformed consent
33. History of another primary malignancy
34. History of active primary immunodeficiency
35. Active infection including tuberculosis (TB) (clinical evaluation that includesclinical history, physical examination and radiographic findings, and TB testing inline with local practice), hepatitis B (known positive Hepatitis B Virus (HBV) surfaceantigen (HBsAg) result), hepatitis C, or human immunodeficiency virus (positive HIV ½antibodies). Patients with a past or resolved HBV infection (defined as the presenceof hepatitis B core antibody (anti-HBc) and absence of HBsAg) are eligible. Patientspositive for hepatitis C (HCV) antibody are eligible only if polymerase chain reactionis negative for HCV RNA.
36. Current or prior use of immunosuppressive medication within 14 days before the firstdose of Durvalumab.
37. Current or prior use of immunostimulatory agents within 14 days before the first doseof Durvalumab.
38. Receipt of live attenuated vaccine within 90 days prior to the first dose of IP. Note:Patients, if enrolled, should not receive live vaccine whilst receiving IP and up to 90 days after the last dose of IP.
39. Female patients who are pregnant or breastfeeding 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.
40. Known allergy or hypersensitivity to Durvalumab or any excipient