Phase III, Open-label, First-line Study of Dato-DXd in Combination With Durvalumab and Carboplatin for Advanced NSCLC Without Actionable Genomic Alterations

1. Participants ≥ 18 years at screening
2. Histologically or cytologically documented NSCLC that at the time of randomisation is Stage IIIB or IIIC disease not amenable to surgical resection or definitive chemoradiation or Stage IV metastatic disease
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 and available therapies (actionable genomic alterations).

Testing is not required for tumors with squamous histology, with exceptions.

1. ECOG PS of 0 or 1
2. Archival tumour tissue
3. Has adequate bone marrow reserve and organ function within 7 days before randomization

Exclusion:

1. Mixed small-cell lung cancer and NSCLC histology; sarcomatoid variant of NSCLC
2. History of another primary malignancy with exceptions
3. Persistent toxicities caused by previous anti-cancer therapy not yet improved to Grade ≤ 1 or baseline, with exceptions.
4. Spinal cord compression or clinically or radiologically active brain metastases
5. History of leptomeningeal carcinomatosis.
6. Known active or uncontrolled hepatitis B or C virus infection.
7. Uncontrolled or suspected infection requiring IV antibiotics, antivirals, or antifungals.
8. Clinically significant corneal disease
9. 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.