MSD (Merck & Co) and Gilead Sciences have terminated a Phase III trial evaluating a duo of blockbuster oncology medicines for non-small cell lung cancer (NSCLC) – marking a setback for the potential commercial expansion of the latter’s drug.
The pair chose to discontinue the KEYNOTE-D46/EVOKE-03 study (NCT05609968) based on a verdict from an external data monitoring committee, which predicted that a combination of Gilead’s antibody-drug conjugate (ADC), Trodelvy (sacituzumab govitecan) plus MSD’s Keytruda (pembrolizumab) would not significantly improve patient overall survival (OS) versus Keytruda alone in patients with frontline, PD-L1-expressing NSCLC.
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Though the Trodelvy-Keytruda combination did demonstrate an additive numerical benefit to progression-free survival (PFS), this value did not reach statistical significance. The therapeutic regimen was well tolerated in the study, with no new safety signals reported.
This Phase III loss will be a notable setback for Gilead, which is looking to broaden Trodelvy’s horizons by exploring its role both in combination and as a monotherapy for the treatment of solid tumours. The California-based pharma noted that the KEYNOTE-D46/EVOKE-03 result would not impact any of these ongoing studies.
With Trodelvy-Keytruda’s hopes dashed in NSCLC, Gilead and MSD will now look to the ASCENT-05 trial (NCT05633654) for a potential victory, which is pitting the two drugs against physician’s choice treatment in patients with high-risk, adjuvant triple negative breast cancer (TNBC).
Gilead is also betting on Trodelvy’s potential as a monotherapy, with the company currently conducting late-stage studies in extensive stage small cell lung cancer (ES-SCLC) and second-line metastatic endometrial cancer.
Currently, US regulators have approved Trodelvy for use in frontline patients with both PD-L1-positive and negative metastatic TNBC. In Q2 2026, Trodelvy’s sales grew 26% year-on-year to $457m, and multiple indication expansions could further drive these sales up in time.
Staving off the Keytruda patent cliff
The KEYNOTE-D46/EVOKE-03 outcome will be a minor setback for MSD, which has invested heavily into R&D for Keytruda in order to expand its role across the oncology treatment paradigm.
Regulators have approved Keytruda in over 20 different types of cancer – making it one of the most broadly approved oncology medicines of all time. However, the drug’s is not likely to hold its position as one of the top-selling medicines for long, as MSD expects the drug will lose market exclusivity in 2028.
With this upcoming milestone, MSD is taking several steps to fortify its pipeline and portfolio. In the realm of oncology, the company is currently pinning its hopes on Kelun Biotech-developed TROP2-targeting ADC, sacituzumab tirumotecan (sac-TMT), which has already secured some Phase III wins in late-stage NSCLC and endometrial cancer. Currently, GlobalData analysts forecast that sac-TMT will reach blockbuster status by 2029.
GlobalData is the parent company of Clinical Trials Arena.
