Phase III, Open-label Study of First-line Osimertinib With or Without Datopotamab Deruxtecan for EGFRm Locally Advanced or metastatic Non-small Cell Lung Cancer - TROPION-Lung14

Exclusion Criteria

• Medical Conditions
• 1. As judged by the investigator, any evidence of diseases (such as severe or uncontrolled systemic diseases, including active bleeding diseases, psychiatric illness/social situations), history of allogenic organ transplant, and/or substance abuse which, in the investigator’s opinion, makes it undesirable for the participant to participate in the study or that would jeopardise compliance with the protocol.
• 2. Refractory nausea and vomiting, chronic gastrointestinal disease, inability to swallow the formulated product, or previous significant bowel resection that would preclude adequate absorption, distribution, metabolism, or excretion of osimertinib.
• 3. History of another primary malignancy.
• 4. Spinal cord compression and unstable brain metastases.
• 5. Clinically significant corneal disease.
• 6. Has active or uncontrolled hepatitis B or C virus infection.
• 7. Known HIV infection that is not well controlled.
• 8. Uncontrolled infection requiring i.v. antibiotics, antivirals or antifungals; suspected infections (eg, prodromal symptoms); or inability to rule out infections (participants with localised fungal infections of skin or nails are eligible).
• 9. Resting ECG with clinically abnormal findings.
• 10. Uncontrolled or significant cardiac disease.
• 11. Past medical history of ILD, drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD.
• 12. Has severe pulmonary function compromise.
• Prior/Concomitant Therapy
• 13. Prior exposure to any agent including an ADC containing a chemotherapeutic agent targeting topoisomerase I, TROP2-targeted therapy.
• Prior/Concurrent Clinical Study Experience
• 14. Participants with a known history of severe hypersensitivity reactions to either Dato-DXd and osimertinib or any excipients of Dato DXd and osimertinib or drugs with a similar chemical structure or class to DXd and osimertinib.