Sacituzumab govitecan-hziy plus pembrolizumab did not demonstrate a statistically significant improvement in progression-free survival compared with pembrolizumab alone as first-line treatment for patients with metastatic non–small cell lung cancer (NSCLC) and a PD-L1 tumor proportion score (TPS) of 50% or greater, according to primary results from the phase III EVOKE-03/KEYNOTE-D46 trial presented at the International Association for the Study of Lung Cancer (IASLC) 2026 World Conference on Lung Cancer (WCLC) (Abstract PL02.06).
In the study, median progression-free survival by blinded independent central review was 11.8 months with sacituzumab govitecan plus pembrolizumab compared with 7.7 months with pembrolizumab alone (hazard ratio [HR] = 0.81, 95% confidence interval [CI] = 0.66–1.00, P = .0252). Although progression-free survival was numerically longer with the combination, the result did not meet the prespecified threshold for statistical significance. At the interim analysis, median overall survival was 21.5 months with sacituzumab govitecan plus pembrolizumab and 22.8 months with pembrolizumab alone (HR = 1.07, 95% CI = 0.85-1.35, P = .7155).
“These findings provide important information as we continue to evaluate treatment strategies for patients with PD-L1–high metastatic NSCLC,” said presenting author Giannis Mountzios, MD, of the Henry Dunant Hospital Center, Athens, Greece.
EVOKE-03/KEYNOTE-D46 is an open-label phase III study that enrolled 620 patients with previously untreated metastatic NSCLC, a PD-L1 TPS of at least 50%, and no EGFR, ALK, or ROS1 alterations. Participants were randomly assigned 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. The dual primary endpoints were progression-free survival by blinded independent central review and overall survival.
The confirmed objective response rate was higher with sacituzumab govitecan plus pembrolizumab than with pembrolizumab alone. The abstract reports an objective response rate of 55.6% for the combination and 43.7% for pembrolizumab alone. The reported disease control rate was 83.3% vs 73.1%, respectively, and median duration of response was 21.4 months vs 21.3 months.
Treatment-related adverse events occurred in 93.2% of patients receiving sacituzumab govitecan plus pembrolizumab and 65.4% of those receiving pembrolizumab alone. Grade 3 or higher treatment-related adverse events occurred in 55.7% and 16.5% of patients, 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.
DISCLOSURE: For full disclosures of the study authors, visit abstractsonline.com.
