Sacituzumab govitecan combined with pembrolizumab did not show a statistically significant improvement in progression-free survival compared with pembrolizumab alone as a first-line treatment for patients with metastatic non-small cell lung cancer and a PD-L1 tumor proportion score of 50% or greater, according to primary results from the Phase 3 EVOKE-03/KEYNOTE-D46 trial. The results were presented at the International Association for the Study of Lung Cancer 2026 World Conference on Lung Cancer.

Median progression-free survival by blinded independent central review was 11.8 months with the combination and 7.7 months with pembrolizumab alone (HR, 0.81; 95% CI, 0.66-1.00; P=0.0252), the release said. While that result was numerically longer for the combination, it did not meet the prespecified threshold for statistical significance. At the interim analysis, median overall survival was 21.5 months with the combination and 22.8 months with pembrolizumab alone (HR, 1.07; 95% CI, 0.85-1.35; P=0.7155).

Giannis Mountzios, M.D., of the Henry Dunant Hospital Center in Athens, Greece, said the combination produced a numerically longer progression-free survival and a higher response rate, but that the trial did not meet statistical significance for its primary PFS endpoint and that overall survival was not significantly improved at the interim analysis. He said the findings provide important information as treatment strategies for patients with PD-L1-high metastatic NSCLC continue to be evaluated.

The confirmed objective response rate was 55.6% for the combination and 43.7% for pembrolizumab alone, according to the abstract. The disease control rate reported in the study table was 83.3% versus 73.1%, and median duration of response was 21.4 months versus 21.3 months. The open-label study enrolled 620 patients with previously untreated metastatic NSCLC, a PD-L1 TPS of at least 50% and no EGFR, ALK or ROS1 alterations, who were randomized to receive sacituzumab govitecan at 10 mg/kg intravenously on days 1 and 8 plus pembrolizumab 200 mg intravenously on day 1 of each 21-day cycle, or pembrolizumab alone.

Treatment-related adverse events occurred in 93.2% of patients receiving the combination and 65.4% of those receiving pembrolizumab alone, the release said, with grade 3 or higher events in 55.7% and 16.5% respectively. The most common treatment-related adverse events in the combination arm included anemia, alopecia, neutropenia, diarrhea and nausea. The safety profile was consistent with the known profiles of the individual agents, with no new or additional toxicities observed with the combination.