Gilead and Merck Scrap Trodelvy-Keytruda Phase 3 in NSCLC After OS Miss

Gilead Sciences (GILD) and Merck (MRK) terminated the Phase 3 KEYNOTE-D46/EVOKE-03 trial of Trodelvy plus Keytruda in first-line PD-L1-positive non-small cell lung cancer on August 6. An external data monitoring committee determined the combination would not significantly improve overall survival versus Keytruda alone. Progression-free survival showed a numerical benefit but did not clear statistical significance. The trial enrolled patients with PD-L1 tumor proportion score of 50% or higher, the population where Keytruda monotherapy already delivers median overall survival exceeding two years.

Gilead closed at $130.86 on August 6, with a market cap of approximately $163 billion. Merck closed at $128.37. Trodelvy generated $457 million in Q2 2026, up 26% year over year, beating the consensus estimate of $448 million. The drug accounted for roughly 6% of Gilead’s $7.8 billion in quarterly product sales. Indication expansion beyond breast cancer was central to the oncology growth narrative.

The NSCLC bar is high. Keytruda monotherapy already delivers durable responses in PD-L1-high patients, and adding a Trop-2 ADC did not clear the survival threshold. The result also clears a lane for Merck’s own sac-TMT (sacituzumab tirumotecan), another Trop-2 ADC from its Kelun partnership. A China-only Phase 3 in PD-L1-negative NSCLC already hit its PFS endpoint, and Merck is evaluating a global registrational strategy. This failure removes a named competitor, making sac-TMT the frontrunner for Merck’s next-generation checkpoint inhibitor backbone in lung cancer.

Trodelvy’s remaining Keytruda combination opportunity is ASCENT-05, an adjuvant triple-negative breast cancer trial evaluating Trodelvy plus Keytruda versus standard of care in patients with residual disease after neoadjuvant therapy. That readout, expected in 2027, is now the event that determines whether the Trodelvy-Keytruda combination has a future beyond the first-line metastatic TNBC indication already approved by the FDA in June 2026 and recommended by the CHMP in July.

The risk: Gilead faces a narrowing oncology path. Trodelvy monotherapy expansion into ES-SCLC and endometrial cancer remains on track, but the NSCLC miss removes a large revenue opportunity. Gilead acquired Trodelvy through its $21 billion Immunomedics acquisition in 2020, and the original investment thesis included lung cancer as a major expansion market. For context on the ADC field and how Trodelvy fits in, see our ADCs explained guide. For a broader look at Gilead’s oncology pipeline, read our coverage of Gilead’s Q2 earnings.

What to watch next: ASCENT-05 adjuvant TNBC data. If that trial misses, the Trodelvy plus Keytruda thesis collapses to the single already-approved metastatic indication.