A Study to Investigate the Efficacy and Safety of Dato-DXd With or Without Osimertinib Compared With Platinum Based Doublet Chemotherapy in Participants With EGFR-Mutated Locally Advanced or Metastatic Non-Small Cell Lung Cancer

What this study is about

This study will assess the effect of Dato-DXd in combination with osimertinib or Dato-DXd monotherapy versus platinum-based doublet chemotherapy in terms of progression-free survival (PFS).

Who can join (things the study team will check)

✅ You may be able to join if…

• Histologically or cytologically confirmed non-squamous NSCLC.
• Must have evidence of documented pre-existing EGFRm information (EGFRm known to be associated with (epidermal growth factor receptor [EGFR] tyrosine kinase inhibitor [TKis] sensitivity [Ex19del, L858R, G719X, S768I, or L861Q], either alone or in combination with other EGFR mutations, which may include T790M).
• Documented extra-cranial radiologic progression on prior osimertinib monotherapy (as most recent line of treatment) in the adjuvant, locally advanced, or metastatic setting.
• Less than or equal to (<=2) prior lines of EGFR TKIs (osimertinib is the only permitted prior third generation EGFR TKI).
• At least one lesion, not previously irradiated, that qualifies as a RECIST v1.1 TL at baseline and can be accurately measured at baseline.
• World Health Organization (WHO)/Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Adequate bone marrow reserve and organ function within 7 days before randomization.

🚫 You may not be able to join if…

• Use of chemotherapy, vascular endothelial growth factor inhibitor, immunotherapy or any anti-cancer therapy in the metastatic setting. Platinum-based chemotherapy in non-metastatic setting within 12 months prior to randomization.
• History of another primary malignancy except for malignancy treated with curative intent with no known active disease within 2 years before the first dose of study intervention.
• Any evidence of severe or uncontrolled systemic diseases, including, but not limited to active bleeding diseases, active infection, active ILD/pneumonitis, cardiac disease.
• Has significant third-space fluid retention (example [eg.], ascites or pleural effusion) as judged by the investigator and is not amenable for required repeated drainage.
• History of non-infectious ILD/pneumonitis including radiation pneumonitis that required steroids or drug-induced ILD, has current ILD/pneumonitis, or has suspected ILD/pneumonitis that cannot be ruled out by imaging at screening.
• Has severe pulmonary function compromise resulting from intercurrent pulmonary illnesses.
• Unstable spinal cord compression and/or unstable brain metastases.
• Participants with symptomatic brain metastases (including leptomeningeal involvement).
• Clinically significant corneal disease.
• Uncontrolled infection requiring systemic antibiotics, antivirals, or antifungals, suspected infections or inability to rule out infections. Use of systemic antibiotics within 14 days of randomization.
• Has known human immunodeficiency virus (HIV) infection that is not well controlled.

Where this trial is running

• Research Site, Fayetteville, Arkansas, United States
• Research Site, Duarte, California, United States
• Research Site, Fountain Valley, California, United States
• Research Site, La Jolla, California, United States
• Research Site, Los Angeles, California, United States
• Research Site, San Diego, California, United States
• Research Site, Colorado Springs, Colorado, United States
• Research Site, Fort Collins, Colorado, United States
• Research Site, Washington D.C., District of Columbia, United States
• Research Site, Gainesville, Florida, United States
• Research Site, Jacksonville, Florida, United States
• Research Site, Athens, Georgia, United States

+ 291 more sites.

Who to contact

AstraZeneca Clinical Study Information Center · 1-877-240-9479 · information.center@astrazeneca.com

It's completely normal to call and ask questions before deciding anything. Mention the study ID: NCT06417814.