Merck and Gilead discontinue phase 3 KEYNOTE-D46/EVOKE-03 study of Trodelvy plus Keytruda in 1L metastatic NSCLC

CAR-T Digest - August 2020

08 June 2026: Merck and Gilead discontinue phase 3 KEYNOTE-D46/EVOKE-03 study of Trodelvy plus Keytruda in 1L metastatic NSCLC

Merck and Gilead have announced the discontinuation of the phase 3 KEYNOTE-D46/EVOKE-03 study evaluating Trodelvy in combination with KEYTRUDA versus KEYTRUDA monotherapy as a first-line treatment for patients with PD-L1-high (TPS ≥50%) metastatic non-small cell lung cancer
The decision followed a recommendation from the study’s independent Data Monitoring Committee after a planned interim analysis concluded that the trial was unlikely to meet its primary endpoint of progression-free survival, despite a numerical improvement being observed in the combination arm
This phase 3 study was designed to evaluate whether the addition of Trodelvy to pembrolizumab could improve outcomes versus pembrolizumab alone in previously untreated metastatic NSCLC patients without EGFR, ALK, or ROS1 genomic alterations
Trodelvy is a first-in-class TROP2-targeted ADC that utilizes a hydrolyzable linker to deliver the topoisomerase I inhibitor payload SN-38, and has been a key component of Gilead’s strategy to expand ADC use beyond breast and urothelial cancers into lung cancer and other solid tumor indications
Strategically, the study discontinuation represents a setback for Trodelvy’s expansion into the first-line NSCLC market and highlights the challenges of translating promising early-stage ADC-immunotherapy combination data into Phase III success, while intensifying focus on competing TROP2-directed programs and alternative ADC-based combination strategies in lung cancer