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).
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).
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.
Parallel
Dato-DXd
DrugDato-DXd will be administered as IV infusion.
Osimertinib
DrugOsimertinib will be administered orally.
Pemetrexed
DrugPemetrexed will be administered as IV infusion.
Carboplatin
DrugCarboplatin will be administered as IV infusion.
Cisplatin
DrugCisplatin will be administered as IV infusion.
Progression free Survival (PFS)
PFS is defined as the time from randomization to Blinded Independent Central Review (BICR)-assessed progression using RECIST v1.1 or death due to any cause, regardless of whether the participant withdraws from study therapy, receives other anti-cancer therapy, or clinical progression.
Overall Survival (OS)
OS is defined as time from randomization until the date of death due to any cause.
Central Nervous System Progression-free Survival (CNS PFS)
CNS PFS is defined as the time from randomization to BICR confirmed progression in the CNS or death due to any cause, regardless of whether the participant withdraws from study therapy, receives other anti-cancer therapy, or clinically progresses prior to BICR confirmed CNS modified RECIST v1.1 progression.
Objective Response Rate (ORR)
ORR is defined as the percentage of participants who have a confirmed complete response (CR) or confirmed partial response (PR), as determined by BICR per RECIST v1.1.
Duration of Response (DoR)
DoR is defined as the time from the date of first documented response until date of documented progression per RECIST v1.1, as assessed by BICR or death due to any cause.
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AstraZeneca
Lead sponsor
Daiichi Sankyo
Collaborator
