FDA and EU Regulators Back Gilead's Trodelvy in First-Line Metastatic Triple-Negative Breast Cancer
FDA approved Trodelvy for first-line metastatic triple-negative breast cancer; EMA's CHMP also recommended Trodelvy plus Keytruda for PD-L1-positive patients. Phase 3 trials showed significant reductions in the risk of disease progression or death.
Gilead Sciences' Trodelvy (sacituzumab govitecan-hziy) has received U.S. Food and Drug Administration (FDA) approval as a first-line treatment for adults with unresectable locally advanced or metastatic triple-negative breast cancer (mTNBC), making it the first antibody-drug conjugate authorized for this setting regardless of PD-L1 status. The European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) has also adopted a positive opinion recommending Trodelvy in combination with Keytruda for adult patients with PD-L1-positive tumors (CPS ≥10) who have not received prior systemic therapy for metastatic disease.
Under the FDA approval, Trodelvy is approved as a single agent for patients who are not candidates for PD-(L)1 inhibitor-based therapy, or in combination with Keytruda or Keytruda Qlex for patients whose tumors express PD-L1 (CPS ≥10). The latest FDA approval comes shortly after the European Commission expanded Trodelvy's label for the same indication, approving Trodelvy as monotherapy for patients with unresectable or metastatic TNBC who have not received prior systemic therapy for metastatic disease and are not candidates for PD-1 or PD-L1 inhibitor therapy. The CHMP's recommendation is based on data from the Phase 3 ASCENT-04/KEYNOTE-D19 study, which demonstrated a 35% reduced risk of disease progression or death with Trodelvy plus Keytruda versus standard-of-care chemotherapy plus Keytruda in PD-L1-positive patients. The European Commission decision on this indication is anticipated later in 2026.
The FDA approval was based on highly statistically significant progression-free survival results from the late-stage ASCENT-03 and ASCENT-04/KEYNOTE-D19 studies. In ASCENT-03, Trodelvy monotherapy reduced the risk of disease progression or death by 38% compared with chemotherapy in patients with PD-L1–ineligible disease, while in ASCENT-04, Trodelvy combined with Keytruda cut the risk by 35% versus Keytruda plus chemotherapy in patients with PD-L1+ disease. Median duration of response reached 12.2 months with Trodelvy versus 7.2 months with chemotherapy in ASCENT-03, and 16.5 months with Trodelvy plus Keytruda versus 9.2 months with Keytruda plus chemotherapy in ASCENT-04.
The National Comprehensive Cancer Network now lists Trodelvy with or without Keytruda as a category 1 preferred first-line treatment option for people with mTNBC across PD-L1 status. Trodelvy is already approved in several countries for second-line or later metastatic TNBC and in more than 50 countries for certain patients with pre-treated HR+/HER2- metastatic breast cancer. With over 75,000 patients treated globally, the new indication expands Trodelvy's clinical utility.
In oncology, Gilead also faced a setback earlier this month, when Merck and Gilead Sciences announced the discontinuation of the phase III KEYNOTE-D46/EVOKE-03 study evaluating Trodelvy in combination with Keytruda as a first-line treatment for patients with metastatic non-small cell lung cancer (NSCLC) whose tumors express high levels of PD-L1 (TPS ≥50%). The decision followed a recommendation from the external Data Monitoring Committee after a pre-specified final progression-free survival analysis and an interim overall survival analysis; the combination showed a numerical improvement in PFS that did not achieve statistical significance, and the committee concluded the likelihood of a statistically significant OS benefit at the final analysis was low.
Separately, Gilead reported positive Phase 3 results from the ISLEND trials for a once-weekly oral HIV regimen combining islatravir and lenacapavir (ISL/LEN). The company's pipeline strategy in 2026 includes an increasing focus on long-acting HIV therapies and oncology, with two significant acquisitions this year: the $7.8 billion buyout of CAR-T company Arcellx and the $3.15 billion buyout of ADC developer Tubulis. Gilead has also invested in oncology through its 2020 acquisition of Immunomedics for $21 billion, which brought Trodelvy into the company; Trodelvy reached blockbuster status in 2023, though Gilead withdrew its 2021 accelerated approval for bladder cancer in 2024 after a confirmatory trial failure.