Merck, Gilead rein in ambitions for Trodelvy in lung cancer after Phase III stumble

Merck (NYSE: MRK) and Gilead Sciences (Nasdaq: GILD) [announced](https://www.businesswire.com/news/home/20260608789974/en/Merck-and-Gilead-Provide-Update-on-Phase-3-KEYNOTE-D46EVOKE-03-Study) the discontinuation of the Phase III KEYNOTE-D46/EVOKE-03 study after [sacituzumab govitecan (Trodelvy) ](https://app.allsci.com/drugs/ASC-DR-0000000035443-1.0-1773147676)— Gilead's Trop-2-directed antibody-drug conjugate (ADC) — failed to produce statistically significant improvement in progression-free survival when added to pembrolizumab (Keytruda) in previously untreated metastatic non-small cell lung cancer (NSCLC) with high PD-L1 expression. The result closes off a meaningful expansion opportunity for sacituzumab govitecan beyond breast cancer and raises broader questions about whether Trop-2-targeted ADCs can add to checkpoint inhibitor monotherapy in a biomarker-selected lung cancer population. The [KEYNOTE-D46/EVOKE-03 study](https://clinicaltrials.gov/study/NCT05609968) was a global, open-label, randomized Phase III trial enrolling approximately 620 patients with previously untreated metastatic NSCLC whose tumors expressed PD-L1 at a tumor proportion score of 50% or higher and lacked sensitizing EGFR, ALK, or ROS1 alterations — the same population for which pembrolizumab monotherapy is already an established standard of care. Patients were randomized 1:1 to receive sacituzumab govitecan (10 mg/kg intravenously on days 1 and 8 of a 21-day cycle) plus pembrolizumab (200 mg intravenously on day 1) or pembrolizumab alone. The trial carried dual primary endpoints of PFS assessed by blinded independent central review and overall survival. Following a pre-specified final PFS analysis and interim OS analysis, the external Data Monitoring Committee recommended discontinuation. A numerical improvement in PFS was observed in the combination arm, but it did not reach statistical significance. Critically, the probability of achieving a statistically significant OS benefit at the planned final analysis was assessed as unlikely. No specific numerical values — median PFS, OS, hazard ratios, or p-values — were disclosed; full data are expected at a future medical meeting. The safety profile of the combination was consistent with the known profiles of each agent individually, and no new safety signals were identified, suggesting tolerability was not the limiting factor. ## Competitive context Pembrolizumab monotherapy in PD-L1-high NSCLC is among the most difficult benchmarks in oncology to beat — the KEYNOTE-024 trial established a durable survival advantage over chemotherapy, and the setting has since attracted multiple failed combination attempts. Regeneron and Sanofi's Libtayo ([cemiplimab](https://app.allsci.com/drugs/ASC-DR-0000000009875-1.0-1757706147)) and Roche's Tecentriq ([atezolizumab](https://app.allsci.com/drugs/ASC-DR-0000000003776-1.0-1757706147)) are also approved as monotherapies in this biomarker-defined population, underscoring how competitive the segment already is. Sacituzumab govitecan holds approved indications in metastatic triple-negative breast cancer and HR-positive, HER2-negative metastatic breast cancer across more than 50 countries, but its lung cancer ambitions now appear significantly narrowed. Cross-trial comparisons are limited by differences in patient selection, trial design, and endpoints, but the pattern of failed combinations in PD-L1-high NSCLC — where monotherapy responses can be durable — suggests the bar for additive benefit is exceptionally high. Gilead has stated there are no changes to ongoing sacituzumab govitecan studies in other tumor types, and full data from KEYNOTE-D46/EVOKE-03 are expected to be presented at a future medical meeting. *** This article was generated with AI assistance and reviewed and edited by the AllSci editorial team Explore more at AllSci News: [https://allsci.com/news/](https://allsci.com/news/) --- Spot something wrong? [Report an issue with this article](https://newsgen-prod.reframedata.com/feedback/sacituzumab-govitecan-trial-discontinued)