Assess the Safety of Immunotherapy Induction With Tremelimumab and Durvalumab Prior to Chemoradiotherapy and/or Resection in the Treatment

Inclusion Criteria:

* Provision of signed, written and dated informed consent prior to any study specific procedures.

  2\. Male or female aged 18 years or older. 3. WHO performance status of 0 or 1. 4. Pathologically proven NSCLC stage III or inoperable stage II (cT1-3N0-1), according to the 8th edition of the AJCC staging, with a clinical indication for concurrent chemo-irradiation. Patients with locoregional recurrent lung tumour following surgery or a second primary cancer are eligible, unless a pneumonectomy was performed.

  5\. Patients should be able to receive concurrent chemo radiotherapy treatment as approved by the MDM.

  6\. Body weight \>30kg 7. Negative pregnancy test (urine or serum) for female patients with childbearing potential; 8. For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of ≤ 1% per year, during the treatment period and for at least 180 days after the last dose of Durvalumab and Tremelimumab combination therapy or 1 month after the last dose of chemotherapy, whichever is later.

A woman is considered to be of childbearing potential if she is postmenarcheal, has not reached a postmenopausal state (≥12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus).

Examples of contraceptive methods with a failure rate of ≤ 1% per year include bilateral tubal ligation, male sterilization, established proper use of hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices (IUDs), and copper IUDs.

The following age-specific requirements apply:

* Women \<50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy).
* Women ≥50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses \>1 year ago, had chemotherapy-induced menopause with last menses \>1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy).

  9\. Adequate organ function. Minimum required laboratory data. 10. No major contra-indications for undergoing EBUS and/or mediastinoscopy. 11. For patients included in the two feasibility cohorts a calculation for the mean lung dose (MLD) for radiotherapy will be performed: in both cohorts at least 2 out of 6 patients with a MLD ≥ 16 need to be included.

Exclusion Criteria:

* 1\. Patients with grade 3 dyspnoea or worse at baseline (according to CTCAE version 4.03).

  2\. Prior radiotherapy to the thorax. 3. Participation in another clinical study with an investigational product during the last 4 weeks.

  4\. Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study or the follow-up period of an interventional study 5. Recent major surgery within 4 weeks prior to entry into the study (excluding the placement of vascular access) that would prevent administration of chemotherapy.

  6\. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirements, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent.

  7\. Presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial.

  8\. Any condition that, in the opinion of the investigator, would interfere with evaluation of the CRT or interpretation of patient safety or study results.

  9\. Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with Durvalumab or Tremelimumab may be included only after consultation with the Study Physician.

  10\. Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[eg, colitis or Crohn's disease\], diverticulitis \[with the exception of diverticulosis\], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome \[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc\]). The following are exceptions to this criterion:
  1. Patients with vitiligo or alopecia
  2. Patients with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement
  3. Any chronic skin condition that does not require systemic therapy
  4. Patients without active disease in the last 5 years may be included but only after consultation with the study physician
  5. Patients with celiac disease controlled by diet alone 11. Subject noncompliance that, in the opinion of the investigator or sponsor, warrants withdrawal; eg, refusal to adhere to scheduled visits 12. General contra-indications for immunotherapy:

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  1. Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice), hepatitis B (known positive HBV surface antigen (HBsAg) result), hepatitis C, or human immunodeficiency virus (positive HIV 1/2 antibodies). Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody \[anti-HBc\] and absence of HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
  2. Receipt of a live, attenuated vaccine within 30 days prior to enrolment or anticipation that such a live, attenuated vaccine will be required during the study.
  3. Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-CTLA-4, anti-PD-1 or anti-PD-L1 therapeutic antibodies.
  4. Treatment with systemic immunostimulatory agents (including but not limited to interferons or IL-2) within 14 days or five half-lives of the drug (whichever is shorter) prior to enrolment. Current or prior use of immunosuppressive medication within 14 days before the first dose of Durvalumab or Tremelimumab. The following are exceptions to this criterion:

     * Intranasal, inhaled, topical steroids, or local steroid injections (eg, intra articular injection)
     * Systemic corticosteroids at physiologic doses not to exceed \<\<10 mg/day\>\> of prednisone or its equivalent
     * Steroids as premedication for hypersensitivity reactions (eg, CT scan premedication)
     * Patients who have received acute, low-dose, systemic immunosuppressant medications (e.g., one-time dose of dexamethasone for nausea) may be enrolled in the study. The use of inhaled corticosteroids for chronic obstructive pulmonary disease, mineralocorticoids (e.g., fludrocortisone) for patients with orthostatic hypotension, and low-dose supplemental corticosteroids for adrenocortical insufficiency are allowed.

       13\. History of idiopathic pulmonary fibrosis (including bronchiolitis obliterans with organizing pneumonia) or evidence of active pneumonitis on screening chest computed tomography scan.

       14\. History of active primary immunodeficiency 15. History of allogeneic transplantation 16. Severe infections within 28 days prior to enrolment, including, but not limited to, hospitalization for complications of infection, bacteraemia, or severe pneumonia or received oral or IV antibiotics within 2 weeks prior to enrolment. Patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or chronic obstructive pulmonary disease) are eligible.