Sacituzumab Govitecan Approved in Europe for First-Line PD-L1 Inhibitor–Ineligible TNBC

The European Commission has granted marketing authorization to sacituzumab govitecan-hziy (Trodelvy) monotherapy for the treatment of adult patients with unresectable or metastatic triple-negative breast cancer (TNBC) who are naive to prior systemic therapy for metastatic disease and are not eligible to receive PD-(L)1 inhibition.¹

This regulatory decision was backed by data from the phase 3 ASCENT-03 trial (NCT05382299), in which patients with TNBC ineligible for PD-L1 inhibitors who received first-line sacituzumab govitecan (n = 279) achieved a statistically significant and clinically meaningful 38% reduction in the risk of disease progression or death vs those who received standard-of-care chemotherapy (n = 279). Data from the primary analysis presented at the 2025 ESMO Congress showed that the median progression-free survival (PFS) by blinded independent central review (BICR) was 9.7 months (95% CI, 8.1-11.1) in the investigational arm vs 6.9 months (95% CI, 5.6-8.2) in the control arm (HR, 0.62; 95% CI, 0.50-0.77; P < .001).² The investigator-assessed median PFS values were 9.6 months (95% CI, 8.3-10.6) and 6.8 months (95% CI, 5.6-7.2), respectively (HR, 0.64; 95% CI, 0.52-0.79).

“This approval brings a profound sense of hope to a community that has long been waiting for progress,” Javier Cortes, MD, PhD, head of the International Breast Cancer Center in Madrid and Barcelona, Spain, stated in a news release.¹ “For women diagnosed with metastatic TNBC, particularly those who are younger, every second counts, and having an effective treatment option that can delay the progression of their disease is invaluable. This is the kind of meaningful advance our community needs.”

The overall response rate (ORR) was 48% (95% CI, 42%-54%) in the sacituzumab govitecan arm vs 46% (95% CI, 40%-52%) in the chemotherapy arm (stratified OR, 1.1; 95% CI, 0.8-1.6).² Additionally, the median durations of response (DORs) in these respective arms were 12.2 months (95% CI, 9.7-13.8) and 7.2 months (95% CI, 5.7-8.4), and the median time to response (TTR) was 1.6 months in both the sacituzumab govitecan (95% CI, 0.7-16.7) and chemotherapy (95% CI, 0.9-6.8) arms. Overall survival (OS) data were not mature at the time of the primary analysis.

Furthermore, patient-reported outcome data from ASCENT-03 presented at the 2025 San Antonio Breast Cancer Symposium (SABCS)showed that physical functioning scores from baseline to week 25 were maintained in the sacituzumab govitecan arm, whereas investigators observed a continuous trend towards physical functioning score deterioration over time in the chemotherapy arm.³ Findings from a detailed safety analysis of ASCENT-03 also presented at SABCS 2025 demonstrated that 99% of patients who received the antibody-drug conjugate (n = 275) experienced any-grade treatment-emergent adverse effects (TEAEs) vs 97% of those who received chemotherapy (n = 276).⁴ The any-grade exposure-adjusted incidence rates were 40.21 (95% CI, 35.58-45.27) vs 21.66 (95% CI, 19.14-24.40), respectively, and 7 fatal TEAEs were reported.

“This approval represents a significant step forward in how we treat [patients] with first-line metastatic TNBC in Europe,” Mika Kakefuda Derynck, MD, senior vice president of Clinical Development in Oncology at Gilead Sciences, added in the news release.¹ “We have long recognized the challenges that patients and clinicians face with this aggressive cancer, and we believe this approval will provide a much-needed new option for [patients] with metastatic TNBC.”

What was the design of ASCENT-03?

This trial enrolled patients with previously untreated, locally advanced inoperable or metastatic TNBC who were not eligible to receive PD-(L)1 inhibition.² Patients were randomly assigned 1:1 to receive intravenous sacituzumab govitecan at 10 mg/kg on days 1 and 8 of each 21-day cycle, or chemotherapy. Eligible patients were offered crossover to second-line sacituzumab govitecan through the study after BICR-confirmed disease progression.

PFS by BICR served as the primary end point. Secondary end points included OS, ORR, DOR, TTR, safety, and quality of life.

What updated data from ASCENT-03 were presented at the 2026 ASCO Annual Meeting?

Data from a prespecified biomarker subgroup analysis of the trial showed that the median PFS with sacituzumab govitecan was longer vs that with chemotherapy across all biomarker subgroups, including BRCA-mutant and wild-type subgroups, HER2 subgroups per immunohistochemistry, and TROP2 expression quartiles.⁵

References

1. European Commission approves Trodelvy as a first-line treatment for metastatic triple-negative breast cancer patients not candidates for PD-(L)1 inhibitors. News release. Gilead. June 23, 2026. Accessed June 23, 2026. https://investors.gilead.com/news/news-details/2026/European-Commission-Approves-Trodelvy-as-a-First-Line-Treatment-for-Metastatic-Triple-Negative-Breast-Cancer-Patients-Not-Candidates-for-PD-l1-Inhibitors/default.aspx
2. Cortés JC, Bardia A, Punie K, et al. Primary results from ASCENT-03: a randomized phase III study of sacituzumab govitecan (SG) vs chemotherapy (chemo) in patients (pts) with previously untreated advanced triple-negative breast cancer (TNBC) who are unable to receive PD-(L)1 inhibitors (PD-[L]1i). Ann Oncol. 2025;36(suppl 2):S1565-S1566. doi:10.1016/j.annonc.2025.09.030
3. Punie K, Tolaney S, Hurvitz S, et al. Patient-reported outcomes (PROs) with sacituzumab govitecan (SG) vs chemotherapy in patients with previously untreated advanced triple-negative breast cancer (TNBC) who are not candidates for PD-(L)1 inhibitors in the phase 3 ASCENT-03 study. Presented at: 2025 San Antonio Breast Conference Symposium; December 9-12, 2024; San Antonio, Texas. RF6-05.
4. Hurvitz A, Bardia A, Tolaney SM, et al. Safety analysis of ASCENT-03, a phase 3 study of sacituzumab govitecan vs chemotherapy for previously untreated advanced triple-negative breast cancer in patients who are not candidates for PD-(L)1 inhibitors. Presented at: 2025 San Antonio Breast Cancer Symposium; December 9-12, 2025; Houston, Texas. Poster PS1-13-24.
5. Barrios C, Hurvitz SA, Tolaney SM, et al. ASCENT-03: efficacy by biomarker subgroup with sacituzumab govitecan (SG) vs chemotherapy (chemo) in participants (pts) with previously untreated advanced triple-negative breast cancer (TNBC) who are not candidates for PD-(L)1 inhibitors (PD-[L]1i). J Clin Oncol. 2026;44(suppl 16):1014. doi:10.1200/JCO.2026.44.16_suppl.1014