Sacituzumab Govitecan-hziy Plus Pembrolizumab Improves PFS in Patients With Metastatic Triple-Negative Breast Cancer

Sacituzumab govitecan-hziy (Trodelvy; Gilead Sciences) plus pembrolizumab (Keytruda; Merck & Co. Inc) met its primary end point in the ASCENT-04/KEYNOTE-D19 study (NCT05382286), demonstrating clinically meaningful improvements in progression-free survival (PFS) in patients with metastatic triple-negative breast cancer (mTNBC) with PD-L1 expression.¹

Illustration of breast cancer cells | Image Credit: © Jack - stock.adobe.com

About 15% of all diagnoses of BC in the United States are TNBC, an aggressive subtype with few treatment choices since tumor cells lack human epidermal growth factor receptor 2, progesterone, and estrogen receptors. Standard chemotherapies, hormone treatments, endocrine therapies, and immunotherapies exhibit little to no response when these receptors are absent. By combining the cytotoxic potential of chemotherapy with the accuracy of monoclonal antibodies, antibody drug conjugates (ADCs), such as sacituzumab govitecan-hziy, offer a revolutionary approach to the treatment of TNBC.²

“For patients with [mTNBC], there is a critical need for more effective treatment options,” Sara Tolaney, MD, MPH, Dana-Farber Cancer Institute and primary investigator of the ASCENT-04 study, said in a press release. “These data suggest that the combination of sacituzumab govitecan-hziy and pembrolizumab may offer a new treatment approach—bringing together a potent antibody drug conjugate with immunotherapy to improve outcomes for patients.”³

SG is an ADC that was first approved by the FDA in 2021 as a monotherapy for patients with unresectable locally advanced or mTNBC who have received 2 or more prior systemic therapies. This decision was based on data from the phase 3 ASCENT trial (NCT02574455), which showed SG therapy yielded greater PFS benefits when compared with single-agent chemotherapy.^2,4

In the global, open-label, randomized phase 3 ASCENT-04 trial, investigators evaluated the efficacy and safety of sacituzumab govitecan in combination with pembrolizumab compared with treatment of chemotherapy plus pembrolizumab in 443 patients with PD-L1-expressing mTNBC. They were randomized 1:1:1 to receive either sacituzumab govitecan at a dosage of 10 mg per kg intravenously on days 1 and 8 of a 21-day cycle plus pembrolizumab at a dosage of 200 mg intravenously on day 1 of a 21-day cycle or chemotherapy (gemcitabine [Gemzar; LillyMedical] plus carboplatin [Paraplatin; Bristol-Myers Squibb], paclitaxel [Abraxane; Abraxis BioScience, LLC], or nab-paclitaxel) plus pembrolizumab. The primary end point was PFS, with secondary end points of overall survival (OS), objective response rate (ORR), duration of response (DOR), time to onset of response (TTR), patient-reported outcomes (PROs), and safety.³

The primary analysis of the trial data revealed that sacituzumab govitecan plus pembrolizumab had superior PFS benefits to the chemotherapy plus pembrolizumab arm. Although the OS data were immature at the time of the PFS analysis, there was an observed early trend improvement compared with the standard of care. The lead investigators also noted that the safety was consistent with the known profiles of sacituzumab govitecan and pembrolizumab.³

“These findings are the first to show the transformative potential of an [ADC] combined with an immuno-oncology agent in early treatment lines of metastatic breast cancer,” Dietmar Berger, MD, PhD, Chief Medical Officer, Gilead Sciences, said in a press release. “For patients with this difficult-to-treat type of breast cancer, these results potentially offer a new pathway that may redefine their treatment options.”³

REFERENCES

1. Study of sacituzumab govitecan-hziy and pembrolizumab versus treatment of physician's choice and pembrolizumab in patients with previously untreated, locally advanced inoperable or metastatic triple-negative breast cancer (ASCENT-04). Updated December 24, 2025. Accessed April 21, 2025. https://clinicaltrials.gov/study/NCT05382286

2. Navigating triple-negative breast cancer treatment with sacituzumab govitecan. Pharmacy Times. February 27, 2025. Accessed April 21, 2025. https://www.pharmacytimes.com/view/navigating-triple-negative-breast-cancer-treatment-with-sacituzumab-govitecan

3. 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. Gilead. April 21, 2025. Accessed April 21, 2025. https://www.gilead.com/news/news-details/2025/trodelvy-plus-keytruda-demonstrates-a-statistically-significant-and-clinically-meaningful-improvement-in-progression-free-survival-in-patients-with-previously-untreated-pd-l1-metastatic-trip

4. Trial of sacituzumab govitecan in participants with refractory/​relapsed metastatic triple-negative breast cancer (TNBC) (ASCENT). Updated June 15, 2022. Accessed April 21, 2025. https://clinicaltrials.gov/study/NCT02574455