Critères d'inclusion : 1. Has pathologically (histologically or cytologically) confirmed NSCLC.
2. Has Stage IIIA, IIIB, or IIIC NSCLC by American Joint Committee on Cancer Version 8.
3. Is unable to undergo surgery with curative intent for Stage III NSCLC as documented by a multidisciplinary tumor board or by the treating physician in consultation with a thoracic surgeon.
4. Has no evidence of metastatic disease, indicating Stage IV NSCLC, in whole-body fluorodeoxyglucose (FDG)-PET or FDG-PET/CT and CT or MRI scans of diagnostic quality of chest, abdomen, pelvis and brain.
5. Has measurable disease as defined by RECIST 1.1, with at least one lesion being appropriate for selection as a target lesion, as determined by local site investigator/radiology review.
6. Has not received prior treatment (chemotherapy, targeted therapy or radiotherapy) for their Stage III NSCLC.
7. Has provided tumor tissue sample (tissue biopsy [core, incisional, or excisional]). FFPE blocks are preferred to slides. Newly obtained tumor sample is highly preferred over archival tissue and should be obtained prior to the thoracic imaging at screening.
8. Has a performance status of 0 or 1 on the ECOG Performance Status assessed within 7 days prior to the first administration of study intervention.
9. Has a life expectancy of at least 6 months.
10. Has adequate PFT defined as a FEV1 >50% of predicted normal volume and the carbon monoxide lung diffusing capacity (DLCO) >40% of predicted normal value. Participants for whom DLCO measurements are not available will be deemed to have adequate oxygen transfer if pulse oximetry (O2 saturation) is determined to be ≥90% on room air.
11. Has adequate organ function; ; all screening laboratory tests
should be performed within 10 days prior to initiation of study intervention.
12. Is male or female of at least 18 years to 120 years of age inclusive, at the time of signing the informed consent.
13. A male participant must agree to use contraception as detailed in Appendix 4 of this protocol during the treatment period and for at least 180 days following the last dose of study intervention.
14. A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least 1 of the following conditions applies:
a. Not a WOCBP
b. A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 180 days following the last dose of study intervention.
15. Has (or legally acceptable representative if applicable) provided written informed consent/assent for the study. The participant may also provide consent/assent for future biomedical research. However, the participant may participate in the main trial without participating in future biomedical research.
Critères de non-inclusion : 1. Has small cell lung cancer or a mixed tumor with presence of small cell elements.
2. Has history, current diagnosis, or features suggestive of MDS/AML.
3. Has had documented weight loss >10% (from baseline) in the preceding 3 months.
4. Has a radiation treatment plan that is likely to encompass a volume of whole lung (total lung V20-GTV) receiving > 20 Gy in total (V20) of more than 34% of lung volume.
5. Has received prior radiotherapy to the thorax, including radiotherapy to the esophagus,mediastinum, or for breast cancer.
6. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX- 40, CD137).
7. Has received prior therapy with olaparib or with any other PARP inhibitor.
8. Had major surgery <4 weeks prior to the first dose of study medication (except for placement of vascular access).
9. Is expected to require any other form of antineoplastic therapy, while on study.
10. Has received a live vaccine within 30 days prior to the first dose of study medication.
11. Has received colony-stimulating factors within 28 days prior to the first dose of study intervention.
12. Is currently receiving either strong or moderate inducers of CYP3A4 that cannot be discontinued for the duration of the study. The required washout period prior to starting olaparib is 5 weeks for pentobarbital and 3 weeks for other agents.
13. Is currently receiving either strong or moderate inhibitors of cytochrome P450 (CYP)3A4 that cannot be discontinued for the duration of the study. The required washout period prior to starting olaparib is 2 weeks.
14. Pemetrexed-specific: Is unable to interrupt aspirin or other NSAIDs, other than an aspirin dose ≤1.3 grams per day, for at least 2 days (5 days for long-acting agents [for example, piroxicam]) before, during, and for at least 2 days after administration of pemetrexed.
15. Pemetrexed-specific: Is unable/unwilling to take folic acid, vitamin B12, and dexamethasone.
16. Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention.
17. Has resting ECG indicating uncontrolled, potentially reversible cardiac conditions, as judged by the investigator or participant has congenital long QT syndrome.
18. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study medication.
19. Has a known additional malignancy that is progressing or has required active treatment within the past 5 years.
20. Has severe hypersensitivity (≥ Grade 3) to study intervention and/or any of its excipients
21. Has an active autoimmune disease that has required systemic treatment in past 2 years (ie, with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed.
22. Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease. Lymphangitic spread of the NSCLC is not exclusionary.
23. Has an active infection requiring systemic therapy.
24. Has a known history of human immunodeficiency virus (HIV) infection. No HIV testing is required unless mandated by local health authority.
25. Has a known history of Hepatitis B (defined as HBsAg reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection.
26. Has active tuberculosis and is receiving treatment.
27. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant’s participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator.
28. In the opinion of the treating investigator, is considered a poor medical risk due to a serious, uncontrolled medical disorder or nonmalignant systemic disease.
29. Has a known psychiatric or substance abuse disorder that would interfere with the participant’s ability to cooperate with the requirements of the study.
30. Is unable to swallow orally administered medication or has a gastrointestinal disorder affecting absorption
31. Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 180 days after the last dose of study intervention.
32. Has had an allogenic tissue/solid organ transplant.