Gilead Advances Trodelvy in Europe With CHMP Nod for First-Line TNBC

Gilead Sciences has received a positive opinion from the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) recommending Trodelvy as a first-line treatment for adults with unresectable locally advanced or metastatic triple-negative breast cancer (TNBC) who are not candidates for PD-1 or PD-L1 inhibitor therapy. The recommendation advances the antibody-drug conjugate toward expanded approval in Europe, with a final European Commission decision anticipated later in 2026.

ASCENT-03 Trial Results

The CHMP opinion is supported by findings from the Phase 3 ASCENT-03 trial (NCT05382299), which evaluated first-line Trodelvy versus physician’s choice chemotherapy in patients with previously untreated metastatic TNBC. The study demonstrated a statistically significant and clinically meaningful improvement in progression-free survival, reducing the risk of disease progression or death by 38% compared with chemotherapy. The safety profile was generally consistent with previously reported Trodelvy studies.

The results reinforce Trodelvy’s potential to shift treatment earlier in the metastatic setting, particularly for patients with limited therapeutic options.

Clinical Context

Metastatic TNBC remains one of the most aggressive breast cancer subtypes, with limited treatment options and poor long-term survival outcomes. Unlike hormone receptor-positive or HER2-positive disease, TNBC lacks established molecular targets, leaving many patients dependent on chemotherapy-based treatment approaches.

Patients who are not eligible for checkpoint inhibitors face an especially restricted therapeutic landscape, making effective first-line therapies critically important because outcomes are often determined early in metastatic disease progression.

Mechanism of Action

Trodelvy is a Trop-2-directed antibody-drug conjugate that delivers SN-38, the active metabolite of irinotecan, directly into tumor cells. Trop-2 is highly expressed across multiple solid tumors, including most breast cancers.

Its hydrolyzable linker also enables a bystander effect, extending cytotoxic activity into the tumor microenvironment and potentially enhancing antitumor efficacy.

Expert Perspective

Dr. Javier Cortes of the International Breast Cancer Center in Madrid and Barcelona said the ASCENT-03 findings support earlier use of sacituzumab govitecan in metastatic TNBC. He noted that treatment decisions made at the first diagnosis of advanced disease can strongly influence long-term outcomes, underscoring the importance of delivering the most effective therapies early in metastatic disease.

Broader Development Program

Beyond ASCENT-03, Gilead has submitted regulatory applications in Europe and the United States for Trodelvy in combination with Keytruda in PD-L1-positive metastatic TNBC, based on data from the Phase 3 ASCENT-04 study.

If approved, Trodelvy could expand across broader first-line metastatic TNBC populations regardless of PD-L1 status, strengthening its role in metastatic breast cancer treatment.

Current Approvals

Trodelvy is already approved in more than 60 countries for previously treated metastatic TNBC and for certain patients with HR-positive/HER2-negative metastatic breast cancer. Since its initial approval in 2020, more than 75,000 breast cancer patients worldwide have received the therapy, reflecting its growing use in oncology practice.

 Reference

Gilead Sciences, Inc. – Gilead Receives CHMP Positive Opinion for Trodelvy® in First-Line Metastatic Triple-Negative Breast Cancer for Patients Not Candidates for PD-(L)1 Inhibitors

Study Details | NCT05382299 | 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 | ClinicalTrials.gov