Sacituzumab govitecan, an antibody-drug conjugate, underperformed in a Phase 3 setting when combined with pembrolizumab in PD-L1-high metastatic lung cancer. The development reported in a closely watched trial failed to demonstrate statistically significant improvement in progression-free survival versus the trial standard. The result is another data point in the ongoing effort to refine ADC–immunotherapy pairing strategies, where previous successes have not consistently translated into broader, randomized trial benefits. For PD-(L)1-high metastatic lung cancer management, the setback limits immediate momentum for this combination and refocuses trial designs on biomarkers and sequencing assumptions that have not yet translated into durable efficacy signals.