A Phase 3 trial evaluating an antibody-drug combination plus immune checkpoint inhibition delivered a clinical letdown in PD-L1-high metastatic lung cancer. Sacituzumab govitecan, an antibody-drug conjugate (ADC), failed to show a statistically significant improvement in progression-free survival when paired with pembrolizumab, challenging a strategy aimed at layering targeted tumor kill with PD-1 blockade.