The FDA approved Trodelvy as a first-line treatment for metastatic triple-negative breast cancer across PD-L1 status, following recent EU approval, based on the Phase 3 ASCENT-03 and ASCENT-04 trials.
Written By: Disha Jadhav, BPharm
Reviewed By: Pharmacally Editorial Team
The U.S. Food and Drug Administration (FDA) has approved Trodelvy (sacituzumab govitecan-hziy) for the first-line treatment of adults with unresectable locally advanced or metastatic triple-negative breast cancer (mTNBC). The approval allows Trodelvy to be used as monotherapy in patients who are not candidates for PD-(L)1 inhibitor-based therapy and in combination with pembrolizumab for patients with PD-L1-positive tumors (combined positive score [CPS] ≥10) identified using an FDA-authorized diagnostic test.
The decision expands Trodelvy’s role in metastatic breast cancer, making it the first approved antibody-drug conjugate (ADC) for first-line mTNBC across PD-L1 status. The drug was previously approved for second-line metastatic TNBC and pre-treated hormone receptor-positive (HR+)/HER2-negative metastatic breast cancer.
Mechanism and Disease Background
Trodelvy is a first-in-class Trop-2-directed antibody-drug conjugate that delivers the topoisomerase I inhibitor SN-38 directly to tumor cells while also producing a bystander effect within the tumor microenvironment. Trop-2 is highly expressed in more than 90% of breast cancers.
Triple-negative breast cancer accounts for approximately 15% of breast cancers and remains the most aggressive subtype. Patients frequently develop early metastatic disease and have limited treatment options. More than half of patients with metastatic TNBC do not receive treatment beyond first-line therapy, underscoring the importance of selecting the most effective initial treatment.
ASCENT-03 Clinical Results
The FDA approval is supported by the Phase 3 ASCENT-03 (NCT05382299) trial, which enrolled patients with previously untreated unresectable locally advanced or metastatic TNBC who were ineligible for PD-(L)1 inhibitor therapy.
Trodelvy monotherapy reduced the risk of disease progression or death by 38% compared with physician’s choice chemotherapy. The treatment also improved median duration of response to 12.2 months versus 7.2 months with chemotherapy.
ASCENT-04/KEYNOTE-D19 Clinical Results
The approval also includes findings from the Phase 3 ASCENT-04/KEYNOTE-D19 (NCT05382286) trial, which evaluated Trodelvy plus pembrolizumab in patients with PD-L1-positive metastatic TNBC. The combination reduced the risk of disease progression or death by 35% compared with pembrolizumab plus chemotherapy and increased the median duration of response to 16.5 months versus 9.2 months, as assessed by blinded independent central review.
Together, the two pivotal studies demonstrated clinically meaningful progression-free survival benefits across both PD-L1-positive and PD-L1-ineligible first-line metastatic TNBC populations.
NCCN Guideline Recommendation
Based on the positive ASCENT-03 and ASCENT-04 findings, the National Comprehensive Cancer Network (NCCN) now recommends Trodelvy, with or without pembrolizumab according to PD-L1 status, as a Category 1 preferred first-line treatment for metastatic TNBC. Trodelvy also retains Category 1 recommendations for second-line metastatic TNBC and previously treated HR-positive/HER2-negative metastatic breast cancer.
More than 75,000 patients across over 60 countries have received Trodelvy since its initial approval, providing extensive clinical and real-world experience with the therapy.
European Commission Approval
The FDA approval follows a recent European Commission authorization of Trodelvy monotherapy for adults with unresectable or metastatic TNBC who have not received prior systemic therapy for metastatic disease and are not candidates for PD-1 or PD-L1 inhibitors. The European approval was also supported by results from the Phase 3 ASCENT-03 (NCT05382299) trial and established Trodelvy as the first antibody-drug conjugate approved in the European Union for first-line metastatic TNBC in this patient population.
Gilead has also submitted a separate European regulatory application seeking approval of Trodelvy in combination with pembrolizumab for patients with PD-L1-positive metastatic TNBC, which remains under review.
Regulatory and Clinical Development
The latest FDA approval establishes Trodelvy as a first-line treatment option for metastatic TNBC regardless of PD-L1 status and further expands the clinical role of Trop-2-directed antibody-drug conjugates. Gilead is continuing global regulatory submissions based on the ASCENT-03 and ASCENT-04 programs while advancing multiple Phase 3 studies evaluating Trodelvy in earlier-stage breast cancer, lung cancer, and gynecologic malignancies.
What This Approval Means for Patients
This approval gives people with metastatic triple-negative breast cancer (mTNBC) a new first-line treatment option that may delay disease progression and provide longer-lasting responses than standard chemotherapy. For the first time, patients can receive a Trop-2-directed antibody-drug conjugate as initial treatment regardless of PD-L1 status, either alone or in combination with pembrolizumab when appropriate. Because many patients with mTNBC do not receive treatment beyond first-line therapy, having a more effective option available at the start of treatment could improve disease control and potentially lead to better long-term outcomes.
Reference
U.S. FDA Approves Trodelvy® for First Line Treatment of Metastatic Triple Negative Breast Cancer
About the Writer
Disha Sanjay Jadhao (LinkedIn) is a pharmacy graduate and healthcare writer with a strong interest in clinical documentation and simplifying healthcare information for better reader understanding. She is enthusiastic, adaptable, and eager to take on new challenges while contributing to clear, accurate, and engaging medical and pharmaceutical content.