Sacituzumab Govitecan Improves PFS in Metastatic TNBC

The phase 3 ASCENT-03 study (NCT05382299) evaluating sacituzumab govitecan-hziy (Trodelvy) for the treatment of first-line metastatic triple-negative breast cancer (TNBC) not eligible for PD-(L)1 inhibition met its primary end point of progression-free survival (PFS).¹

The antibody-drug conjugate sacituzumab govitecan led to a statistically significant and clinically meaningful improvement in PFS compared with chemotherapy, and the safety profile of the agent was consistent with prior studies. Data for overall survival (OS) were not mature at the time of this analysis, but no OS detriment was observed.

“The ASCENT-03 outcome represents the first clinically meaningful advance for this patient population in over 20 years [vs] chemotherapy,” said Dietmar Berger, MD, PhD, chief medical officer, Gilead Sciences, in a press release. “By addressing this aggressive and difficult to treat disease earlier, we can potentially improve treatment options for the high unmet need that patients with metastatic triple-negative breast cancer face.”

Full data from ASCENT-03 will be presented at an upcoming medical meeting and shared with regulatory authorities. Data from ASCENT-04 (NCT05382286) evaluating sacituzumab govitecan plus pembrolizumab (Keytruda) will be presented as a late-breaking abstract during the American Society of Clinical Oncology (ASCO) Annual Meeting held May 30 to June 3, 2025, in Chicago, Illinois. Gilead announced in April 2025 that ASCENT-04 had met its primary end point of PFS and showed early improvement in OS in patients with inoperable locally advanced or metastatic TNBC with tumor PD-L1 expression.²

“Almost half of the patients diagnosed with metastatic triple-negative breast cancer do not receive treatment beyond first-line, demonstrating an urgent need for innovative treatment options in this early setting,” said Javier Cortes, MD, head of the International Breast Cancer Center in Spain and principal investigator of the ASCENT-03 study in the press release.¹ “Traditional chemotherapy has been the standard of care for early treatment of metastatic triple-negative breast cancer, and we know that therapeutic advances in this disease area serve a critical unmet need for patients and the broader oncology community.”

About ASCENT-03

The phase 3 ASCENT-03 study enrolled an estimated 540 patients across 516 global sites with locally advanced inoperable or metastatic TNBC.³ Patients were required to have tumors that were PD-L1–negative at screening or could not be treated with a PD-L1 inhibitor and must have completed treatment for stage I to III breast cancer or present with de novo metastatic disease. Patients were also required to have an ECOG performance status of 0 or 1 and adequate organ function.

Patients were randomly assigned to receive sacituzumab govitecan 10 mg/kg on days 1 and 8 of a 21-day cycle or physician’s choice of paclitaxel, nab-paclitaxel, or gemcitabine.

Along with the primary end point of PFS and key secondary end point of OS, additional secondary end points include objective response rate, duration of response, time to response, percentage of patients experiencing treatment-emergent adverse events, percentage of patients experiencing clinical laboratory abnormalities, and change in baseline in quality of life.

The estimated primary completion date of the study is July 2028.

REFERENCES:

1. ASCENT-03: Trodelvy® demonstrates highly statistically significant & clinically meaningful improvement in progression free survival in patients with first-line metastatic triple-negative breast cancer who are not candidates for checkpoint inhibitors. News release. Gilead Sciences, Inc. May 23, 2025. Accessed May 27, 2025. https://tinyurl.com/37yv34pe

2. Trodelvy® plus Keytruda® demonstrates a statistically significant and clinically meaningful improvement in progression free survival in patients with previously untreated PD-L1+ metastatic triple-negative breast cancer. News release. Gilead Sciences, Inc. April 21, 2025. Accessed May 27, 2025. https://tinyurl.com/mpetbxmp

3. Study of sacituzumab govitecan-hziy versus treatment of physician's choice in patients with previously untreated locally advanced inoperable or metastatic triple-negative breast cancer (ASCENT-03). ClinicalTrials.gov. Updated May 18, 2025. Accessed May 27, 2025. https://clinicaltrials.gov/study/NCT05382299