IPH5201 and Durvalumab in Patients With Resectable Non-Small Cell Lung Cancer (MATISSE)

Inclusion criteria Patients are eligible to be included in the study only if all of the following criteria apply: 1. Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the Informed Consent Form (ICF) and in this protocol. 2. Provision of signed and dated written ICF prior to any mandatory study specific procedures, sampling, and analyses - including collection of samples for genetic analysis, if applicable. 3. Patients must be ≥18 years at the time of screening. 4. Newly diagnosed and previously untreated patients with histologically or cytologically documented NSCLC. Patients should have resectable disease (Stage IIA to Stage IIIA; Stage IIIB - Nodal stage N2 after the first 40 patients \[cohort 2\]), according to Version 8 of IASLC Staging Manual in Thoracic Oncology (2016), and be candidates for lobectomy, sleeve resection, or bilobectomy at the time of screening. For patients with N2 disease, only those with 1 single nodal station ≤3 cm are eligible (only valid for Cohort 1). At screening, complete surgical resection of the primary NSCLC must be deemed achievable, as assessed by a multidisciplinary evaluation, which must include a thoracic surgeon who performs lung cancer surgery as a prominent part of his/her practice. * T4 tumors will only be eligible if they are defined as T4 based only on their size (more than 7 cm); any other reason for T4 (e.g., adherent to any of the following structures: diaphragm, mediastinum, heart, great vessels, trachea, recurrent laryngeal nerve, esophagus, vertebral body, carina) will be considered ineligible. * Nodal status should be investigated with whole-body fluorodeoxyglucose-positron emission tomography (FDG-PET), plus contrast-enhanced CT. If PET/CT scan is positive in the mediastinum, or if the scan is negative but there is T \>3 cm, central tumor, or cN1, then it is recommended that nodal status be proven by biopsy via endobronchial ultrasound, mediastinoscopy, or thoracoscopy. 5. WHO Performance Status (WHO PS) score or Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 0 or 1 at enrollment. 6. Adequate organ and marrow function as defined below: * Hemoglobin ≥9.0 g/dL. * Absolute neutrophil count (ANC) ≥1.5 × 109/L. * Platelet count ≥100 × 109/L. * Serum bilirubin ≤1.5 × Upper limit of normal (ULN). This will not apply to patients with confirmed Gilbert's syndrome, who will be allowed upon consultation with their physician. * Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 × ULN. * Measured creatinine clearance (CrCL) \>40 mL/min or calculated CrCL \>40 mL/min as determined by Cockcroft-Gault formula using actual body weight (Cockroft-Gault, 1976) (https://www.kidney.org/professionals/KDOQI/gfr\_calculatorCoc). 7. Must have a life expectancy of at least 12 weeks. 8. Body weight \>35 kg. 9. Male or female. Women of childbearing potential should use an acceptable method of contraception from the time of screening throughout the total duration of the study, and (for drugs that are potentially genotoxic) the drug washout period (180 days after the last dose of study drugs) to prevent pregnancy. A non-sterilized male partner of a woman of childbearing potential must use a male condom plus spermicide (or condom alone in countries where spermicides are not approved) throughout this period. Male patients who intend to be sexually active with a female partner of childbearing potential must be surgically sterile or using an acceptable method of contraception (from the time of screening throughout the total duration of the study and (for drugs that are potentially genotoxic) the drug washout period (180 days after the last dose of study drugs) to prevent pregnancy in a partner. Male patients must not donate or bank sperm during this same time period. For more details on contraceptive guidance of the study for both women of childbearing potential and non sterilized male patients. 10. Negative pregnancy test (serum or urine) for women of childbearing potential. 11. Provision of tumor samples (newly acquired \[preferred\] or archival tumor tissue \[≤6 months old\]) to confirm PD-L1 status, epidermal growth factor receptor (EGFR), or anaplastic lymphoma kinase (ALK) status, where required during screening and prior to nC1D1. (a) PD-L1 status: (i) If the patient's PD-L1 status has already been assessed using the analytically validated Ventana PD-L1 (SP263) immunohistochemistry (IHC) assay, 22C3 PharmDx assay, or 28-8 PharmDx assay, this test result can be used. (ii) Local laboratory results can be used if performed using the analytically validated Ventana PD-L1 (SP263) IHC assay, 22C3 PharmDx assay, or 28-8 PharmDx assay (iii) If appropriate local testing and/or previous results are not available, PD-L1 testing using the Ventana PD-L1 (SP263) IHC assay will be performed centrally using either newly acquired tumor tissue (preferred) or archival tissue (≤6 months old). Note: For Cohort 2 (PD-L1-positive cohort), only patients with PD-L1 expression tumor proportion score (TPS) ≥1% will be enrolled. (b) ALK and EGFR status: (i) Local laboratory results for ALK and EGFR will be obtained using a well validated, local-regulatory-approved assay. Neither patients with EGFR/ALK mutations nor those with unknown EGFR/ALK status will be enrolled, with the following exceptions: * Patients with documented Kirsten rat sarcoma virus (KRAS) mutations do not require EGFR/ALK status. * Patients with squamous cell carcinoma do not require ALK status. 12. Provision of tumor samples appropriate for exploratory biomarker analyses 13. Patients are suitable for inclusion if the planned surgery is lobectomy, sleeve resection, or bilobectomy, as determined by the attending surgeon based on the baseline findings. Patients whose planned surgery at enrollment includes pneumonectomy, segmentectomies, or wedge resections are not eligible for this study. 14. A pre- or post-bronchodilator forced expiratory volume (FEV1) of 1.0 L and diffusing capacity of lung for carbon monoxide (DLCO) \>40% postoperative predicted value. Use of these cut-off values to assess candidacy for resection should be guided by the results of cardiopulmonary exercise testing as outlined in the European Society for Medical Oncology (ESMO) guidelines on pre-treatment risk assessment. Both an FEV1 and a DLCO test are required for assessing lung function at screening. Exclusion Criteria Patients meeting any of the following exclusion criteria will not be eligible to participate in the study: 1. Patients with sensitizing EGFR mutations or ALK translocations. 2. History of allogeneic organ transplantation. 3. 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 \[e.g., granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, or uveitis\]). 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/Medical Scientist. * Patients with celiac disease controlled by diet alone. 4. Uncontrolled intercurrent illness, including but not limited to, uncontrolled hypertension, unstable angina pectoris, uncontrolled cardiac arrhythmia, active interstitial lung disease (ILD), 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. 5. History of any grade of venous or arterial thromboembolic events including cerebrovascular accident, transient ischemic attack, or unstable angina pectoris within 6 months prior to enrollment. 6. History of another primary malignancy, except for the following: * Malignancy treated with curative intent and with no known active disease ≥5 years before the first dose of study drugs and of low potential risk for recurrence. * Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease. * Adequately treated carcinoma in-situ without evidence of disease. 7. Patients with small-cell lung cancer or mixed small-cell lung cancer. 8. History of active primary immunodeficiency. 9. Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and tuberculosis testing in line with local practice), hepatitis B (known positive hepatitis B surface antigen \[HBsAg\] result) and hepatitis C virus (HCV). Patients with a past or resolved hepatitis B virus (HBV) infection (defined as the presence of hepatitis B core antibody and absence of HBsAg) are eligible. Patients positive for HCV antibody are eligible only if the polymerase chain reaction test is negative for HCV RNA. 10. Patients who have preoperative radiotherapy treatment as part of their care plan. 11. Patients who require or may require pneumonectomy, segmentectomies, or wedge resections, as assessed by their surgeon, to obtain potentially curative resection of primary tumor. 12. QTc interval ≥470 ms (Note: If prolonged, then 2 additional electrocardiograms \[ECGs\] should be obtained and the average QTcF interval should be used to determine eligibility). 13. Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients. 14. Any medical contraindication to treatment with chemotherapy as listed in the local labelling. 15. Patients with moderate or severe cardiovascular disease: * Presence of cardiac disease, including myocardial infarction or unstable angina pectoris within 6 months prior to study entry. * New York Heart Association (NYHA) Class III or IV congestive heart failure, or uncontrolled hypertension. * History of hypertensive crisis/hypertensive encephalopathy within 6 months prior to the scheduled first dose of study drugs. 16. Any concurrent chemotherapy, investigational product, biologic or hormonal therapy for cancer treatment. However, concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable. 17. Receipt of live attenuated vaccine within 30 days prior to the first dose of study drugs. Note: If enrolled, patients should not be administered live vaccine while receiving study drugs and up to 30 days after the last dose of study drugs. 18. Major surgical procedure (as defined by the Investigator) within 30 days prior to the first dose of study drugs. 19. Prior exposure to immune-mediated therapy including, but not limited to, other anti-CTLA-4, anti-PD-1, anti-PD-L1, and anti-PD-L2 antibodies. Patients who received agents targeting the adenosine pathway (e.g., anti-CD73 antibody, adenosine A2A receptor \[A2AR\] inhibitor, anti-CD39 antibody) are also excluded. 20. Current or prior use of immunosuppressive medication within 14 days before the first dose of study drugs. The following are exceptions to this criterion: * Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra-articular injection) * Systemic corticosteroids ≤12 mg/day of prednisone or its equivalent * Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication) 21. Participation in another clinical study with an investigational product administered within 30 days prior to enrollment. 22. Previous study drugs (durvalumab, IPH5201) assignment in the present study. Other Exclusions 23. Female patients who are pregnant or breastfeeding, or male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 180 days after the last dose of study drugs administration. 24. Involvement in the planning and/or conduct of the study (applies to both company staff and/or staff at the study site). 25. Judgment by the Investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions, and requirements. 26. Exclusion criteria for participation in the optional (DNA) genetics research component of the study include the following: * Previous allogeneic bone marrow transplant * Non-leukocyte-depleted whole blood transfusion within 120 days before genetic sample collection. 27. Only for patients in Cohort 2: Patients with PD-L1 expression TPS \<1% or unknown PD-L1 status.