Efficacy and Safety of CRT, Durvalumab and Surgery for SST

Inclusion Criteria:

1. A definite diagnosis of non-small cell lung cancer has been obtained by biopsy fromthe primary lesion.

2. Meet all of the following (UICC-TNM classification 8th edition). I. Regarding theprimary lesion, meet one of the following on chest CT. i. Direct invasion of the chestwall at or above the height of the first rib (at least invasion of the parietalpleura) ii. Direct invasion of the subclavian artery or vein II. Regarding regionallymph nodes, meet either of the following by chest CT and FDG-PET/CT. Metastasis isalso considered if lymph node metastasis is determined by either chest CT orFDG-PET/CT. i. cN0 ii. cN1 and no metastases to #10, #11, and #12 lymph nodes iii. cN3 (ipsilateral supraclavicular lymph node metastasis) and no metastases in regionallymph nodes (N1 and N2) other than "#13, #14 lymph nodes" III. No distant metastases (including intrapulmonary metastases in the same ling lobe and in a different lunglobe on the same side) on imaging tests including FDG-PET/CT

3. It is judged that radical resection is possible by lobectomy (including bilobectomyfor 2 lobes), which satisfies the following [1] and [2]. I. The board respiratory surgeon judges that none of the following is true based onthe image findings. i. There is vertebral body infiltration that requires total spondylectomy ii. Presenceof spinal cord infiltration iii. Invaded trachea or tracheal bifurcation iv. Invasionof aortic arch or ascending aorta v. Invading brachial plexus at C8 or higher vi.Esophageal infiltration that requires esophageal reconstruction for resection vii.Pneumonectomy is required for radical resection II. Meet all of the following. i.Predicted postoperative forced expiratory volume of 1 second (FEV1.0) ≥ 800 mL within 56 days before registration ii. SpO2 > 93% (room air) with the latest inspection valuewithin 14 days before registration

4. Consult with the radiotherapy doctor and it is judged that all of the following aremet. I. Radiation therapy is possible according to the protocol II. The irradiation fielddoes not reach the hilum

5. The age of the registration date is 20 years or older and 75 years or yonger.

6. Performance status (PS) is 0 or 1 according to ECOG standards (PS must be described inmedical records)

7. The presence or absence of measurable lesions is not required.

8. No history of following surgery irrespective of whether for a benign or malignantlesion. I. Thoracoscopic surgery or thoracotomy with excision of the affected lung oresophagus or mediastinum (however, a history of thoracoscopic surgery without wedgeresection or lung, esophagus, or mediastinal resection (eg, pleural biopsy)) isallowed) II. Median sternotomy surgery (with or without organ resection) III.Pulmonary resection other than wedge resection of the contralateral lung (whetheropen-heart surgery or thoracoscopic surgery)

9. There is no history of chemotherapy, including treatment for other cancer types (including molecular targeted therapies and immune checkpoint inhibitors). However,the history of drug therapy as adjuvant therapy is allowed if it was completed morethan 3 years ago. In addition, a history of hormone therapy for other cancer types isallowed.

10. If there is a history of radiotherapy including other cancer types, the lung, hilum,mediastinum, and supraclavicular fossa are not included in the irradiation field.

11. Chest CT does not show interstitial pneumonia or pulmonary fibrosis.

12. No history of complication of autoimmune disease or chronic or recurrent autoimmunedisease. However, patients with type 1 diabetes which is well controlled byappropriate treatment, hyperthyroidism/hypothyroidism that requires only antithyroiddrug/hormone replacement therapy, autoimmune skin disease that does not requiresystemic treatment (Pemphigus, psoriasis vulgaris, pemphigus vulgaris, vitiligo), andceliac disease controlled only by dietary control are regarded as eligible if theyhave been inactive in the past 5 years, even with a history of autoimmunecomplications or history.

13. No surgical treatment with general anesthesia within 14 days (2 weeks) beforeregistration.

14. No systemic administration of steroids, other immunosuppressive drugs, orimmunoglobulins within 28 days (4 weeks) before registration. However, those that meetthe following conditions are allowed. I. Intranasal/inhalation/topical steroid injection or local steroid injection (forexample, intra-articular injection) II. Systemic administration of steroid drugs at adose of 10 mg/day or less in terms of prednisolone III. Steroids as premedication (egCT premedication)

15. Can be taken orally.

16. No ischemic changes were observed on the latest 12-lead ECG within 28 days beforeregistration. However, if a 12-lead electrocardiogram shows ischemic changes,echocardiography, exercise electrocardiography, etc. should be performed, and if it isjudged that new treatment for ischemic heart disease is not necessary, it isqualified.

17. The latest inspection value within 14 days before registration (possible on the sameday two weeks before the registration date) satisfies all of the following. I. White blood cell count ≧4,000/mm3 II. Hemoglobin ≥ 11.0 g/dL (no blood transfusionwithin 14 days before the blood sampling date of the test used for registration) III.Platelet count ≧10×104 /mm3 IV. Total bilirubin ≤ 2.0 mg/dL V. AST ≤ 75 U/L VI. ALT ≤ 75 U/L VII. Serum creatinine ≤ 1.2 mg/dL

18. Written informed consent from the patient to participate in the study.

19. The attending physician can judge that the enrolled patients understand the treatmentand evaluation schedule of this study and can comply with them.

Exclusion Criteria:

1. Having active double cancer (simultaneous double cancer/multiple cancer andmetachronous double cancer/multiple cancer with a disease-free period of 3 years orless, even if the disease-free period is less than 3 years, clinical The 5-yearrelative survival rate is similar to that of stage I prostate cancer, clinical stage 0completely responded to radiation therapy, stage I laryngeal cancer, and completeexcision of the following pathological stage cancers. History of cancer equivalent to 95% or more is not included in active double cancer/multiple cancer). Gastric cancer "adenocarcinoma (general type)": Stage 0-I, colon cancer (adenocarcinoma): Stage 0-I,rectal cancer (adenocarcinoma): Stage 0-I, esophageal cancer (squamous cell carcinoma,glandular) Squamous cell carcinoma, basal cell carcinoma): Stage 0, breast cancer (non-invasive ductal carcinoma, lobular carcinoma): Stage 0, breast cancer (invasiveductal carcinoma, lobular invasive carcinoma, Paget's disease): 0 Stage-IIA,endometrial cancer (endometrioid adenocarcinoma, mucinous adenocarcinoma): Stage I,prostate cancer (adenocarcinoma): Stage I-II, cervical cancer (squamous cellcarcinoma): Stage 0, thyroid cancer (Papillary cancer, follicular cancer): stage I,stage II, stage III, renal cancer (clear cell carcinoma, chromophobe cell carcinoma):stage I, non-melanoma skin cancer, malignant melanoma without a definite diagnosis,etc. Lesions of intramucosal cancer

2. Has an infectious disease that requires systemic treatment (including active pulmonarytuberculosis).

3. When registering, a fever of 38.0°C or higher is generated.

4. Women who are pregnant, possibly pregnant, within 28 days of delivery, orbreastfeeding. A man who wants a partner to become pregnant. Or a reproductive male orfemale patient who is not willing to use an effective contraceptive by Week 13 (Day

91. after the last dose of durvalumab (see 6.4.7.).

5. Participation in the study is considered to be difficult due to the combination ofmental illnesses or symptoms that impair daily life.

6. Continuous systemic administration (oral or intravenous) of steroid drugs or otherimmunosuppressive drugs in excess of 10 mg/day in terms of prednisolone.

7. With uncontrolled diabetes.

8. With uncontrolled hypertension.

9. A gastrointestinal disorder accompanied by uncontrolled diarrhea.

10. With unstable angina (angina with onset or exacerbation of attack within the last 3weeks) or a history of myocardial infarction within 6 months.

11. Poor valvular heart disease, dilated cardiomyopathy, hypertrophic cardiomyopathy,congestive heart failure, and arrhythmia.

12. Chest CT reveals severe emphysema.

13. Either HBs antigen, HCV antibody, or HIV1/2 antibody is positive.

14. Continuous use of flucytosine (Ancotil®) is required.

15. Participating in another clinical trial (excluding observational studies) during the 6months prior to enrollment.

16. A history of allogeneic organ transplant.

17. A history of active primary immunodeficiency.

18. Live vaccines (BCG, polio, measles-rubella mixture, measles, rubella, mumps,chickenpox, yellow fever, rotavirus, etc.) have been administered within 30 daysbefore registration.

19. Has hypersensitivity or allergy to the test drug or its additives used in this test.