Study of Datopotamab Deruxtecan (Dato-DXd) in Combination With Durvalumab and Carboplatin for First-Line Treatment of Patients With Advanced NSCLC Without Actionable Genomic Alterations

1. Participants ≥ 18 years at screening
2. Participants with histologically or cytologically documented NSCLC that is Stage IIIB or IIIC disease not amenable for surgical resection or definitive chemoradiation or Stage IV metastatic NSCLC disease at the time of randomisation, who have not received prior chemotherapy or other systemic therapy for first-line Stage IIIB, IIIC or IV
3. Lacks sensitising EGFR tumour tissue mutation and ALK and ROS1 rearrangements and has no documented tumour genomic alterations in NTRK, BRAF, RET, MET or other actionable driver oncogenes with approved therapies (actionable genomic alterations).
4. ECOG PS of 0 or 1
5. Archival tumour tissue collected prior to signing of ICF
6. Has adequate bone marrow reserve and organ function within 7 days before randomisation

Exclusion:

1. History of another primary malignancy except for malignancy treated with curative intent with no known active disease within 3 years before the first dose of study intervention and of low potential risk for recurrence
2. Mixed small-cell lung cancer and NSCLC histology; sarcomatoid variant of NSCLC
3. Persistent toxicities caused by previous anti-cancer therapy not yet improved to Grade ≤ 1 or baseline (with exceptions)
4. Active or prior documented autoimmune, connective tissue or inflammatory disorders (with exceptions)
5. Spinal cord compression or brain metastases unless asymptomatic, stable, not requiring steroids for at least 7 days prior to randomisation, and a minimum of 2 weeks have elapsed between the end of radiotherapy and study enrollment
6. History of leptomeningeal carcinomatosis
7. Clinically significant corneal disease
8. Known active or uncontrolled hepatitis B or C virus infection
9. Known HIV infection that is not well controlled
10. History of non-infectious ILD/pneumonitis that required steroids, has current ILD/pneumonitis, or has suspected ILD/pneumonitis that cannot be ruled out by imaging at screening