Phase III Study to Determine Efficacy of Durvalumab in Stage II-III Non-small Cell Lung Cancer (NSCLC) After Curative Intent Therapy.

Inclusion Criteria:

Informed consent

1. Capable of giving signed informed consent which includes compliance with therequirements and restrictions listed in the ICFs and in the protocol.

2. Provision of signed and dated, written informed consent form prior to any mandatorystudy-specific procedures, sampling, and analyses.

3. Provision of signed and dated written optional genetic informed consent prior tocollection of the optional sample for genetic analysis. This consent should besigned at the time of second screening. This optional sample and analyses areseparate from the mandatory genetic testing consent included in ICF1. The following criteria must have been met at the time of surgery or at the time ofthe curative intent therapy (first screening):

4. Age ≥18 years at the time of screening (ICF1);

5. Male and/or female

6. Histologically confirmed NSCLC with resectable stage II-III disease who haveundergone curative intent therapy (complete resection of the primary tumor ±neoadjuvant and/or adjuvant therapy) per SoC. Select stage IIIB (ie, T3N2 or T4N2) patients will be eligible, provided they areupstaged to T3N2 or T4N2 based on confirmed pathology after surgery. Patients whoare staged as T3N2 or T4N2 prior to surgery are not eligible.

7. A contrast-enhanced CT/MRI scan of the chest and abdomen (including liver andadrenal glands) along with brain MRI (preferred) or brain CT with IV contrast musthave been done for surgical planning prior to surgery. It is recommended thatpatients undergo combined FDG-PET (18F-Fluoro-deoxyglucose positron emissiontomography) and CT scan (computerized tomography) within the 6 weeks prior tosurgery in order to rule out detectable extrathoracic, extracranial metastasis andto assess for potential mediastinal lymph node involvement prior to surgery. If thepositron emission tomography (PET) scan was not performed, or data from a PET is notavailable, patients may still be enrolled into the study provided appropriateimaging (CT/MRI) is performed prior to randomization.

8. Complete resection of the primary NSCLC is mandatory. Invasive (pre-operative orintra-operative) exploration of hilar and mediastinal lymph nodes must have beenperformed to confirm primary tumor nodal status (prior to or after surgery).Surgical resection of the primary NSCLC can occur by open thoracotomy or byvideo-assisted thoracic surgery (VATs) and resection can be achieved bysegmentectomy, lobectomy, sleeve resection, bilobectomy or pneumonectomy. Patientsundergoing wedge resection are not eligible for this study. Criteria for prior systemic chemotherapy/radiotherapy:

9. Patients should have completed (or be undergoing) curative intent therapy (surgery ±neoadjuvant and/or adjuvant therapy; adjuvant therapy can include PORT) withexceptions noted below: Patients who discontinue chemotherapy and/or PORT for toxicity prior to completionof all planned therapy are eligible. Patients who have not received any neoadjuvant and/or adjuvant chemotherapy, andmeet all other eligibility criteria, may be eligible under the followingcircumstances:

• All patients who are eligible for adjuvant chemotherapy MUST be offeredadjuvant chemotherapy.

• The patient has declined adjuvant chemotherapy, and in the opinion of theInvestigator, this is the patient's final decision after receiving appropriateinformation and adequate time to make the decision. The patient's refusal ofadjuvant chemotherapy must be documented.

• If in the view of the Investigator, adjuvant chemotherapy is contraindicateddue to an underlying intercurrent illness/laboratory abnormality, which is notconsidered reversible within a reasonable timeframe for the patient to beeligible for adjuvant therapy, which must be documented. Criteria assessed prior to and at the start of surveillance:

10. Confirmation of suitable biosamples for WES and central PD-L1 testing. Resectedtumor tissue and whole blood samples must be provided to the diagnostic laboratoryfor WES of tumor and germline DNA, respectively as soon as possible followingpathology confirmation. Samples must be sent no later than 1-2 weeks aftercompletion of adjuvant therapy or 3-5 weeks after surgery (if no adjuvant therapy isgiven) for development of the Sponsor-approved personalized panel for MRD detectionat a central reference laboratory. Germline sequencing of whole blood is mandatory.Resected tumor tissue must also be provided for PD-L1 testing at a central referencelaboratory (see inclusion criteria 15).

11. Post-adjuvant therapy or post-surgery (if no adjuvant therapy is given) CT scan ofthe chest and abdomen (including liver and adrenal glands) and brain MRI [preferred]or brain CT with IV contrast should be available to confirm no evidence ofmetastasis. If scans were not performed post-curative intent therapy, additionalscans must be done prior to start of surveillance.

12. Consents to be accessible for q6w±3d plasma sample collection for MRD evaluation andfor q12w±1w CT scans during the 96-week surveillance period.

13. The plasma sample that marks the start of surveillance must be collected 8±1 weeksafter completion of adjuvant therapy (if administered) or 12±1 weeks after surgery (where adjuvant therapy is not given).

• A patient who is determined to be MRD- based on analysis of this plasma sample (ie, MRD- at the start of surveillance) may continue in surveillance providedall other eligibility criteria are met.

• A patient who is determined to be MRD+ based on analysis of this plasma sample (ie, MRD+ at the start of surveillance) may be eligible for immediaterandomization provided all other eligibility criteria are met. A patient who becomes MRD+ during surveillance is eligible to enter the secondscreening period and may be randomized in the study if all other eligibilitycriteria are met. Criteria for second screening prior to randomization to treatment:

14. CT scan of the chest and abdomen (including liver and adrenal glands) and brain MRI [preferred] or brain CT with IV contrast performed within the 28 days ± 7 days priorto randomization to confirm no evidence of RECIST 1.1-defined disease recurrenceand/or metastasis.

15. Known tumor PD-L1 status determined at a central reference laboratory testingservice using a validated Ventana SP263 PD-L1 immunohistochemistry (IHC) assay priorrandomization. Patients with unknown PD-L1 status are not eligible for the study.

16. WHO/Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1.

17. Complete post-operative wound healing must have occurred prior to randomization;patients must have recovered from all acute, reversible toxic effects from priortreatments (excluding alopecia) that could potentially adversely impact furtheradministration of durvalumab/placebo according to the Investigator's judgment.

18. Must have recovered from all acute, reversible toxic effects from chemotherapy thatcould potentially adversely impact further administration of durvalumab or placeboaccording to the Investigator's judgment

19. Adequate organ and marrow function as described in the protocol.

20. Must have a life expectancy of at least 12 weeks Weight

21. Body weight >30 kg Inclusion criteria assessed prior to entering the observationperiod

22. No evidence of RECIST 1.1-defined disease recurrence or metastasis confirmed by CTscan of the chest and abdomen (including liver and adrenal glands) and a brain MRI (preferred) or brain CT with IV contrast.

23. MRD- status, as determined by testing the last plasma sample collected during the 96-week surveillance period.

Exclusion Criteria:

Diagnostics assessments:

1. EGFR and/or ALK mutant as assessed either from the tumor biopsy taken prior tosurgery or the resected tumor tissue. Testing must be performed using awellvalidated, local regulatory-approved test. EGFR/ALK may be tested centrally iflocal testing is unavailable.

2. Mixed small cell and NSCLC histology.

3. Require re-resection or are deemed to have unresectable NSCLC by amultidisciplinaryevaluation that must include a thoracic surgeon who performs lung cancer surgery asa significant part of their practice.

4. Baseline imaging demonstrating unequivocal evidence of RECIST 1.1-defined diseaserecurrence or evidence of clinical recurrence outside of imaging prior torandomization. In the event of lymphadenopathy on imaging that would lead toexclusion, histopathological confirmation of lymph node metastasis should beobtained prior to excluding a patient from the study. If pathological confirmationof lymph node metastasis is not technically feasible and imaging appearance aredeemed unequivocal for relapse, the patient will be excluded. Medical conditions

5. History of allogeneic organ or bone marrow transplantation.

6. Non-leukocyte-depleted whole blood transfusion in 120 days of genetic samplecollection

7. Active or prior documented autoimmune or inflammatory disorders (includinginflammatory bowel disease [eg, colitis or Crohn's disease], diverticulitis [withthe exception of diverticulosis], systemic lupus erythematosus, Sarcoidosissyndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoidarthritis, hypophysitis, uveitis, etc]). The following are exceptions to thiscriterion: Patients with vitiligo or alopecia Patients with hypothyroidism (eg, followingHashimoto syndrome) stable on hormone replacement Any chronic skin condition thatdoes not require systemic therapy Patients without active disease in the last 5years may be included but only after consultation with the Study Physician Patientswith celiac disease controlled by diet alone

8. Uncontrolled intercurrent illness, including but not limited to, ongoing or activeinfection, symptomatic congestive heart failure, uncontrolled hypertension, unstableangina pectoris, uncontrolled cardiac arrhythmia, active ILD, serious chronicgastrointestinal conditions associated with diarrhea, or psychiatric illness/socialsituations that would limit compliance with study requirement, substantiallyincrease risk of incurring AEs or compromise the ability of the patient to givewritten informed consent.

9. History of another primary malignancy except for Malignancy treated with curativeintent and with no known active disease ≥5 years before the first dose of IP and oflow potential risk for recurrence Adequately treated non-melanoma skin cancer orlentigo maligna without evidence of disease Adequately treated carcinoma in-situwithout evidence of disease

10. History of active primary immunodeficiency

11. Active infection including tuberculosis (clinical evaluation that includes clinicalhistory, physical examination and radiographic findings, and tuberculosis testing inline with local practice), hepatitis B virus (HBV) (known positive HBV surfaceantigen (HBsAg) result), hepatitis C virus (HCV), 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 ofHBsAg) are eligible. Patients positive for HCV antibody are eligible only ifpolymerase chain reaction is negative for HCV RNA.

12. Known allergy or hypersensitivity to any of the IPs or any of the IP excipientsPrior/concomitant therapy

13. Received any IO therapy in the adjuvant setting or any prior exposure to durvalumab.

14. Received any radiotherapy in the neoadjuvant setting.

15. Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment.Concurrent use of hormonal therapy for non-cancer-related conditions (eg, hormonereplacement therapy) is acceptable.

16. Radiotherapy treatment to more than 30% of the bone marrow or with a wide field ofradiation within 4 weeks of the first dose of IP.

17. Receipt of live attenuated vaccine within 30 days prior to the first dose of IP.Note: Patients, if enrolled, should not receive live vaccine while receiving IP andup to 30 days after the last dose of IP.

18. Major surgical procedure (as defined by the Investigator) within 28 days prior tothe first dose of IP.

19. Current or prior use of immunosuppressive medication within 14 days before the firstdose of IP. 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 toexceed 10 mg/day of prednisone or its equivalent Steroids as premedication forhypersensitivity reactions (eg, CT scan premedication) Prior/concurrent clinicalstudy experience

20. Previous IP assignment in the present study

21. Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of aninterventional study

22. Prior randomization or treatment in a previous durvalumab clinical study regardlessof treatment arm assignment. Other exclusions

23. Female patients who are pregnant or breastfeeding.

• Female patients who become pregnant during the study will be withdrawn fromsurveillance and are not eligible for randomization.

24. Male or female patients of reproductive potential who are not willing to employeffective birth control at the time of entry into second screening (initiated withthe signing of ICF2a) until 90 days after the last dose of IP (See Appendix H).

25. Judgment by the Investigator that the patient should not participate in the study ifthe patient is unlikely to comply with study procedures, restrictions, andrequirements