Gilead Wins CHMP Backing for Trodelvy® in First-Line Metastatic TNBC Treatment
Gilead Sciences has announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency has adopted a positive opinion recommending the approval of Trodelvy as a monotherapy for adult patients with unresectable locally advanced or metastatic triple-negative breast cancer (TNBC) who have not previously received systemic therapy for metastatic disease and are not eligible for PD-1 or PD-L1 inhibitor treatment.
The recommendation marks an important regulatory milestone for Trodelvy and could significantly expand treatment options for patients with one of the most aggressive forms of breast cancer. A final decision from the European Commission regarding the proposed additional indication is expected later in 2026.
Triple-negative breast cancer accounts for a smaller proportion of all breast cancer diagnoses but is widely considered among the most difficult subtypes to treat. Unlike other forms of breast cancer, TNBC lacks expression of estrogen receptors, progesterone receptors, and HER2 proteins, limiting the effectiveness of many targeted therapies commonly used in breast cancer treatment. As a result, patients with metastatic TNBC often face fewer therapeutic options and poorer survival outcomes compared with other breast cancer populations.
The urgency surrounding treatment decisions in metastatic TNBC is especially critical in the first-line setting. For many patients, initial therapy may represent the best opportunity to achieve disease control before cancer progression limits future treatment possibilities. This makes the availability of more effective first-line therapies particularly important for improving long-term outcomes.
According to Gilead, the CHMP’s positive opinion is supported by findings from the Phase 3 ASCENT-03 clinical trial, which evaluated Trodelvy as a first-line treatment for patients with metastatic TNBC who are not candidates for PD-1 or PD-L1 inhibitor therapies.
The study demonstrated a statistically significant and clinically meaningful improvement in progression-free survival when compared with standard-of-care chemotherapy. Specifically, Trodelvy reduced the risk of disease progression or death by 38% in the patient population studied.
Researchers and oncology experts believe the results could represent a major advancement in how metastatic TNBC is treated in Europe, particularly for patients who have limited therapeutic options due to ineligibility for immunotherapy.
“Metastatic TNBC remains one of the most challenging breast cancer subtypes to treat, particularly at the time of first diagnosis of advanced disease, when therapeutic options are limited for many patients,” said Javier Cortes, who serves as Head of the International Breast Cancer Center in Madrid and Barcelona, Spain.
Dr. Cortes stated that the CHMP’s positive opinion for sacituzumab govitecan represents an important step toward potential approval in this treatment setting and reflects the clinically meaningful outcomes seen in the ASCENT-03 study. He emphasized that introducing more effective therapies earlier in the disease course is essential to improving outcomes for patients living with metastatic TNBC.
Trodelvy is an antibody-drug conjugate (ADC) directed at Trop-2, a protein commonly expressed in several cancers, including triple-negative breast cancer. ADCs are designed to deliver targeted cancer therapy directly to tumor cells while limiting exposure to healthy tissue. Trodelvy has already established a significant presence in metastatic breast cancer treatment, particularly in later-line settings.
Currently, Trodelvy is approved for patients with previously treated metastatic TNBC as well as for patients with pre-treated HR-positive/HER2-negative metastatic breast cancer. According to Gilead, more than 75,000 breast cancer patients across over 60 countries have been treated with Trodelvy since its launch in 2020, giving healthcare providers substantial real-world clinical experience with the therapy.
The company also noted that Trodelvy remains the only Trop-2-directed antibody-drug conjugate to demonstrate meaningful overall survival benefits in both second-line or later metastatic TNBC and pre-treated HR-positive/HER2-negative metastatic breast cancer.
In addition, Trodelvy is currently the only ADC to achieve positive results in four Phase 3 clinical trials focused on HER2-negative metastatic breast cancer. These results have strengthened its position as a potentially important treatment platform across multiple breast cancer settings.
“This CHMP positive opinion for Trodelvy represents a pivotal moment for people with metastatic TNBC across Europe, and we look forward to hearing from the European Medicines Agency,” said Mika Kakefuda Derynck, Senior Vice President of Clinical Development, Oncology at Gilead Sciences.
Dr. Derynck explained that the recommendation builds upon the extensive clinical experience already gained with Trodelvy in later treatment lines and could potentially transform how physicians approach first-line treatment for certain metastatic TNBC patients. She noted that introducing an effective treatment earlier in the care journey may offer patients a better chance for improved disease management and outcomes.
Beyond the current CHMP recommendation, Gilead is also pursuing additional regulatory approvals involving Trodelvy in combination with Keytruda for patients with PD-L1-positive unresectable locally advanced or metastatic TNBC.
These applications are based on data from the Phase 3 ASCENT-04 study and have been submitted to both the European Medicines Agency and the U.S. Food and Drug Administration. The regulatory submissions are currently under review.
If approved, the combination of Trodelvy and Keytruda could broaden the role of Trodelvy in first-line metastatic TNBC treatment regardless of PD-L1 status. This would potentially position Trodelvy as a foundational therapy across a wider spectrum of TNBC patients.
Despite the encouraging clinical data and regulatory progress, Gilead emphasized that the use of Trodelvy as a monotherapy for first-line metastatic TNBC patients who are not candidates for PD-1 or PD-L1 inhibitors remains investigational until formal regulatory approvals are granted. Likewise, the combination of Trodelvy and pembrolizumab for PD-L1-positive metastatic TNBC is still under evaluation, and the safety and efficacy of these treatment approaches have not yet been fully established by regulatory authorities.
The CHMP recommendation nevertheless represents a significant development for patients and clinicians seeking improved options in metastatic TNBC, an area of oncology that continues to face substantial unmet medical needs.
For many healthcare professionals, the potential expansion of Trodelvy into earlier lines of treatment could redefine standards of care for metastatic TNBC patients across Europe. As research continues to evolve, the focus remains on providing therapies capable of extending survival while improving disease control and quality of life for patients facing aggressive breast cancer diagnoses.
The upcoming European Commission decision later this year will determine whether Trodelvy gains formal approval for this additional indication, potentially opening the door for broader patient access across European markets.
About Triple-Negative Breast Cancer
TNBC is the most aggressive type of breast cancer and has historically been difficult to treat, accounting for approximately 15% of all breast cancers. TNBC disproportionally impacts younger, premenopausal, and Black and Hispanic women. TNBC cells do not have estrogen and progesterone receptors and have limited HER2 expression. Due to the nature of TNBC, treatment options are extremely limited compared with other breast cancer types.
TNBC has a higher chance of recurrence and metastases than other breast cancer types. The average time to metastatic recurrence for TNBC is approximately 2.6 years compared with 5 years for other breast cancers, and the relative five-year survival rate is much lower. Among women with metastatic TNBC, the five-year survival rate is 12%, compared with 28% for those with other types of mBC.
About Trodelvy
Trodelvy (sacituzumab govitecan-hziy) is a first-in-class Trop-2-directed antibody-drug conjugate. Trop-2 is a cell surface antigen highly expressed in multiple tumor types, including in more than 90% of breast and lung cancers. Trodelvy is intentionally designed with a proprietary hydrolyzable linker attached to SN-38, a topoisomerase I inhibitor payload. This unique combination delivers potent activity to both Trop-2 expressing cells and the tumor microenvironment through a bystander effect.
Trodelvy is currently approved in more than 60 countries for second-line or later metastatic triple-negative breast cancer (TNBC) and in more than 50 countries for certain patients with pre-treated HR+/HER2- metastatic breast cancer (mBC). Outside of Europe, Gilead has submitted supplemental applications to the U.S. Food and Drug Administration (FDA) for approval of Trodelvy based on the ASCENT-03 and ASCENT-04 studies.
Trodelvy is currently being evaluated in multiple ongoing Phase 3 trials across a range of tumor types with high Trop-2 expression. These studies with Trodelvy, both in monotherapy and in combination with pembrolizumab, involve earlier lines of treatment for TNBC and HR+/HER2- breast cancer—including in curative settings—as well as in lung and gynecologic cancers, where previous proof-of-concept studies have demonstrated clinical activity.
