Sacituzumab Govitecan Improves PFS in 1L PD-1/PD-L1 Inhibitor Ineligible mTNBC

In the phase 3 ASCENT-03 trial, sacituzumab govitecan did not show an OS detriment vs chemotherapy in previously untreated metastatic triple-negative breast cancer.

Sacituzumab govitecan-hziy (Trodelvy) demonstrated a clinically meaningful and statistically significant improvement in progression-free survival (PFS), meeting the primary end point of the phase 3 ASCENT-03 trial (NCT05382299), compared with chemotherapy in patients with first-line metastatic triple-negative breast cancer (TNBC) who are not candidates for PD-1/PD-L1 inhibitors, according to a press release from the developer, Gilead Sciences.1

At the time of this analysis, the key secondary end point of overall survival (OS) was not yet mature, though no OS detriment was observed. The safety profile of sacituzumab govitecan was consistent with previously observed studies, and no new safety signals were identified.

Currently, sacituzumab govitecan is approved for the treatment of patients with pretreated, unresectable, locally advanced or metastatic TNBC and pretreated, unresectable, locally advanced or metastatic hormone receptor–positive, HER2-negative breast cancer.2,3

More thorough results from the ASCENT-03 trial will be shared at a future medical meeting; there are also plans to hold discussions with regulatory agencies. The investigators noted that the use of sacituzumab govitecan in first-line metastatic TNBC is still investigational and that neither safety nor efficacy has been confirmed with the agent.

“Almost half of the patients diagnosed with metastatic TNBC do not receive treatment beyond first line, demonstrating an urgent need for innovative treatment options in this early setting,” stated Javier Cortes, MD, PhD, 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 TNBC, and we know that therapeutic advances in this disease area serve a critical unmet need for patients and the broader oncology community.”

ASCENT-03 is a randomized, open-label trial comparing the PFS difference from treatment with sacituzumab govitecan vs treatment of physician’s choice in patients with previously untreated, locally advanced or metastatic TNBC whose tumor cells do not express PD-L1 or in those previously treated in early settings with anti–PD-L1 agents whose tumors express PD-L1.

The trial randomly assigned approximately 540 patients in a 1:1 ratio to receive either 10 mg/kg of sacituzumab govitecan on days 1 and 8 of a 21-day cycle or treatment of physician’s choice consisting of gemcitabine plus carboplatin, paclitaxel, or nab-paclitaxel. Those who progressed on chemotherapy were permitted to cross over to sacituzumab govitecan.

Eligible patients had previously untreated, locally advanced or metastatic TNBC and measurable disease based on CT or MRI per RECIST v1.1.4 Additionally, patients had an ECOG performance status of 0 or 1 and adequate organ function.

Those who received systemic anticancer treatment within the previous 6 months or radiation therapy within 2 weeks of enrollment, had not recovered from adverse effects of a previously administered agent, had previously received topoisomerase I inhibitors, had active second malignancy, and had active serious infection requiring antibiotics were ineligible for enrollment.

The trial’s primary end point was PFS per blinded independent central review. Secondary end points included OS, objective response rate, duration of response, time to response, patient-reported outcomes, and safety.

“The ASCENT-03 outcome represents the first clinically meaningful advance for this patient population in over 20 years vs chemotherapy,” stated Dietmar Berger, MD, PhD, chief medical officer at Gilead Sciences, in the press release.1 “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 TNBC face.”

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. May 23, 2025. Accessed May 27, 2025. https://tinyurl.com/kzckwdbw
2. FDA grants regular approval to sacituzumab govitecan for triple-negative breast cancer. FDA. April 7, 2021. Accessed May 27, 2025. https://tinyurl.com/393unvyp
3. U.S. FDA approves Trodelvy in pre-treated HR+/HER2- metastatic breast cancer. News release. Gilead. February 3, 2023. Accessed May 27, 2025. https://bwnews.pr/3Y0bftX
4. 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://tinyurl.com/5c5tbyz8