A single center, single arm, phase 1 / 2 trial

RT will be applied to the primary tumor in 1 fraction of 8Gy, followed by one dose of durvalumab.

Resection is planned approximately 4 weeks after the RT and durvalumab administration.

safety defined as the percentage of patients with adverse events.

major pathological response (MPR) and pathological complete response (pCR) rates in resected tumor-specimens.

tumor immune infiltration after durvalumab and RT in 4 categories

radiological response to durvalumab and RT using RECIST v1.1 criteria, and metabolic response based on 18F-FDG PET

Histologically confirmed NSCLC

T1c-3N0, here T3 tumors are based on size, but not based on invasion into the thoracic wall, mediastinum, vertebra or diaphragm or ipsilateral lung nodules

Willing and able to provide written informed consent for the trial

Above 18 years of age on day of signing informed consent

Have measurable disease based on RECIST 1.1

Have a ECOG performance status of 0-1, and are considered operable based on pulmonary function test and/or exercise testing

Demonstrate adequate organ function, as deemed acceptable by the treating physician in the context of immunotherapy
Body weight >30 kg

Prior surgery and/or radiotherapy on the ipsilateral thorax

Patients deemed inoperable

Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of day 0. Inhaled or topical steroids, and adrenal replacement steroid >10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease

Additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy

Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., 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:

• Patients with vitiligo or alopecia
• Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement
• Any chronic skin condition that does not require systemic therapy Patients without active disease in the last 5 years may be included but only after consultation with the study physician
• Patients with celiac disease controlled by diet alone
• Uncontrolled intercurrent illness, including but not limited to 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 requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent
• Active infection requiring systemic therapy
• A history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies)
• Active infection including tuberculosis, hepatitis B, hepatitis C
• Psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
• Has received prior therapy with an anti-PD-1, anti-PD-L1 including durvalumab, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways
• Patient is pregnant or breastfeeding, or expecting to conceive within the projected duration of the trial, starting with the pre-screening or screening visit through 23 weeks after the last dose of trial treatment.