A closely watched Phase 3 trial failed to show added benefit for combining the antibody-drug conjugate sacituzumab govitecan with pembrolizumab in first-line PD-L1–high metastatic lung cancer. The study reported no statistically significant improvement in progression-free survival. The result is a setback for a strategy that has been explored across solid tumors: pairing an ADC with checkpoint inhibition to intensify immune-mediated tumor killing and extend control. Clinically, the finding narrows the set of frontline options in PD-L1–high metastatic disease and shifts attention to alternative ADC–immunotherapy pairings, sequencing, or biomarker-enriched approaches. For the market, the data reduce near-term enthusiasm for this exact combination while highlighting how difficult it remains to translate preclinical synergy into Phase 3 outcomes.