Trodelvy Outperforms Chemo in ASCENT-03 TNBC Trial

Highlights

• Gilead’s Trodelvy met its primary endpoint in the ASCENT-03 trial, outperforming chemotherapy in delaying progression or death in previously untreated mTNBC patients who are not candidates for immunotherapy.
• The drug maintained a favorable safety profile with no new adverse signals.
• Trodelvy's recent success follows its combination win with Keytruda in PD-L1-positive TNBC in the ASCENT-04 trial.
• Gilead is positioning Trodelvy as a potential foundational treatment for all first-line mTNBC patients, regardless of PD-L1 status.
• Despite clinical progress, Trodelvy faces competition from AstraZeneca/Daiichi Sankyo’s Datroway and Merck/Kelun-Biotech’s sac-TMT.
• 2024 sales totaled $1.3 billion, with first-quarter 2025 sales dipping to $293 million due to inventory dynamics; peak sales projections range from $2.9 billion to $3.2 billion by 2030.

Gilead’s Antibody-Drug Conjugate Hits Primary Endpoint in ASCENT-03 Trial

Gilead Sciences’ antibody-drug conjugate (ADC) Trodelvy has achieved a significant milestone as a standalone treatment in metastatic triple-negative breast cancer (TNBC), following its recent success in combination with Merck & Co.’s Keytruda. The company announced that the late-stage ASCENT-03 trial met its primary endpoint, demonstrating that Trodelvy outperformed standard chemotherapy in delaying disease progression or death.

According to Gilead, the trial targeted patients with previously untreated metastatic TNBC who are not eligible for PD-1 or PD-L1 inhibitors. These patients either lack PD-L1 protein expression or are otherwise unsuitable for immunotherapy. As the company explained in its announcement on Friday, the results showed a “highly statistically significant and clinically meaningful” improvement in progression-free survival (PFS), underscoring the therapy’s value for this difficult-to-treat population.

Positive Safety Profile Maintained

Gilead confirmed that Trodelvy’s safety profile in ASCENT-03 was consistent with findings from earlier studies, with no new safety concerns identified. Although overall survival (OS) data remains immature, the company noted that no detrimental impact on OS has been observed to date.

“The ASCENT-03 outcome represents the first clinically meaningful advance for this patient population in over 20 years versus chemotherapy,” said Dr. Dietmar Berger, Gilead’s recently appointed Chief Medical Officer. “By addressing this aggressive and difficult to treat disease earlier, we can potentially improve treatment options for the high unmet need that patients with metastatic triple-negative breast cancer face.”

Success Across PD-L1-Positive and Negative Populations

The solo success of Trodelvy builds on its earlier combination win in the ASCENT-04 trial, where it was paired with Keytruda. That trial showed the combo was superior to Keytruda and chemotherapy alone in previously untreated PD-L1-positive TNBC patients. Gilead plans to present detailed ASCENT-04 findings at the upcoming American Society of Clinical Oncology (ASCO) meeting.

With promising data in both PD-L1-positive and negative populations, Gilead stated that Trodelvy “has the potential to be the backbone treatment for all patients across first-line mTNBC.”

Market Competition and Strategic Trials Continue

Despite the promising clinical data, Trodelvy faces mounting competition. AstraZeneca and Daiichi Sankyo’s Datroway received FDA approval in January for HR-positive, HER2-negative breast cancer, entering the same TROP2 ADC class. Meanwhile, Kelun-Biotech and Merck’s sacituzumab tirumotecan (sac-TMT) was approved in China in November, adding further competitive pressure.

Gilead has encountered setbacks in Trodelvy’s clinical development, which have somewhat diminished the asset’s initial appeal as a cornerstone of the company’s oncology pipeline. Nonetheless, Gilead is actively pursuing additional trials across various breast cancer subtypes. For instance, the ASCENT-07 study is investigating Trodelvy in HER2-negative breast cancer following endocrine therapy, while ASCENT-05 is evaluating its use in early-stage TNBC.

Sales Outlook and Analyst Expectations

In financial terms, Trodelvy generated $1.3 billion in sales in 2024, marking a 24% year-over-year increase. However, the drug experienced a 5% sales decline in the first quarter of 2025, attributed to inventory fluctuations. Despite this dip, Trodelvy is projected to reach peak sales of around $2.9 billion by 2030, with Citi analysts suggesting the figure could climb to $3.2 billion.