Gilead’s Trodelvy Plus Keytruda Significantly Improves Progression-Free Survival in PD-L1-Positive Metastatic Triple-Negative Breast Cancer

Image Credit: Adobe Stock Images/Lars Neumann

Topline findings from Gilead’s Phase III ASCENT-04/KEYNOTE-D19 study found that the combination of Trodelvy (sacituzumab govitecan-hziy) and Keytruda (pembrolizumab) significantly improved progression-free survival (PFS) compared to Keytruda plus chemotherapy in patients with previously untreated, PD-L1-positive (CPS ≥ 10) metastatic triple-negative breast cancer (mTNBC). Full results from the study will be presented at an upcoming medical meeting.¹

“These findings are the first to show the transformative potential of an antibody-drug conjugate combined with an immuno-oncology agent in early treatment lines of metastatic breast cancer,” said Dietmar Berger, MD, PhD, chief medical officer, Gilead Sciences, 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.”

The global, open-label, randomized ASCENT-04/KEYNOTE-D19 study evaluated the efficacy and safety of Trodelvy plus Keytruda in 443 patients across multiple sites. Participants were randomly assigned in a 1:1 ratio to receive 10 mg/kg of Trodelvy on days one and eight of a 21-day cycle with 200 mg of Keytruda on day one, or chemotherapy plus Keytruda. Chemotherapy options included gemcitabine plus carboplatin, paclitaxel, or nab-paclitaxel.

The trial’s primary endpoint was PFS as determined by blinded independent central review. Secondary endpoints included overall survival, objective response rate, duration of response, time to onset of response, patient-reported outcomes, and safety.

No new safety signals were observed with the combination regimen, with reports of adverse events (AEs) consistent with the known profiles of each agent in their approved indications. Common AEs included decreased leukocyte and neutrophil counts, anemia, diarrhea, nausea, lymphopenia, fatigue, alopecia, constipation, hyperglycemia, hypoalbuminemia, vomiting, decreased appetite, reduced creatinine clearance, elevated alkaline phosphatase, and electrolyte imbalances, including low magnesium, potassium, and sodium.

Trodelvy is currently approved in over 50 countries for second-line or later treatment of mTNBC, and in over 40 countries for pre-treated HR+/HER2- metastatic breast cancer (MBC). Gilead is actively investigating Trodelvy in multiple Phase III trials targeting HER2-negative MBC subtypes. These include the ASCENT-03 trial for the first-line treatment of patients with mTNBC who are not candidates for PD-L1-based therapy, ASCENT-05 in early-stage TNBC, and ASCENT-07 in HR+/HER2- MBC patients post-endocrine therapy. Trodelvy is also being evaluated in Phase III studies in lung and gynecological cancers.¹

According to the American Cancer Society, approximately 316,950 new cases of invasive breast cancer are expected to be diagnosed in the United States by the end of 2025, with an estimated 42,170 deaths. One in eight women in the United States will develop breast cancer in their lifetime. Although incidence rates have risen by around 1% in recent years, mortality declined by 44% between 1989 and 2022, largely due to improved screening and treatment. The median age at diagnosis is 62 years, though cases can occur in women younger than 45 years of age.²

“For patients with metastatic triple-negative breast cancer, there is a critical need for more effective treatment options,” said Sara Tolaney, MD, MPH, Dana-Farber Cancer Institute, primary investigator, ASCENT-04 study, in the 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.”

Trodelvy is currently the only Trop-2-directed antibody-drug conjugate with demonstrated survival benefit in both mTNBC and HR+/HER2- MBC. It has received Category 1 preferred status in the National Comprehensive Cancer Network guidelines for both indications.¹

References

1. 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

2. Key Statistics for Breast Cancer. American Cancer Society. Accessed April 21, 2025. https://www.cancer.org/cancer/types/breast-cancer/about/how-common-is-breast-cancer.html