A first-line phase 3 trial reported that sacituzumab govitecan plus pembrolizumab did not significantly improve progression-free survival in metastatic PD-L1-high lung cancer. The result marks a setback for an approach that had shown activity across multiple tumor settings and was widely watched as a potential expansion path. From a development standpoint, the negative readout narrows the near-term label and combination strategy options for PD-L1-high disease and may prompt reassessment of patient selection, sequencing, and mechanism-based biomarkers for future ADC–IO trials.