Emerging Antibody-Drug Conjugate Combinations in EGFR-Mutated NSCLC

August 20, 2026

This segment defines what a new second-line regimen must deliver in EGFR-mutated advanced non-small cell lung cancer: improvement on the progression-free survival benchmark set by MARIPOSA-2 and the TROPION-Lung studies, an overall survival signal, intracranial activity given how often these patients progress in the central nervous system, and a manageable toxicity burden after multiple prior lines. ORCHARD, in which osimertinib was added to datopotamab deruxtecan, stands out as encouraging enough to support continuing the tyrosine kinase inhibitor rather than dropping it, largely for central nervous system control, though the trial is single-arm and tested more than one dose. Sacituzumab tirumotecan was studied as monotherapy in OptiTROP-Lung04. Overlapping toxicity favors combining an antibody-drug conjugate with a tyrosine kinase inhibitor rather than with chemotherapy.