Gilead's Trodelvy-Keytruda Combo Shows Promise in First-Line Triple-Negative Breast Cancer Treatment

Gilead Sciences has announced a significant breakthrough in the treatment of triple-negative breast cancer (TNBC), with its antibody-drug conjugate (ADC) Trodelvy showing promising results when combined with Merck's immunotherapy drug Keytruda. This development marks a potential shift in the treatment landscape for one of the most aggressive forms of breast cancer.

Trodelvy-Keytruda Combination Outperforms Standard of Care

In a phase 3 trial known as Ascent-04 or Keynote-D19, the combination of Trodelvy (sacituzumab govitecan) and Keytruda (pembrolizumab) demonstrated superior efficacy compared to the current standard of care in first-line treatment for metastatic TNBC patients with PD-L1 positive tumors. The study, which enrolled over 440 patients, showed a significant improvement in progression-free survival (PFS) for the Trodelvy-Keytruda combination versus Keytruda plus chemotherapy.

Dr. Dietmar Berger, Gilead's chief medical officer, emphasized the groundbreaking nature of these findings, stating, "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."

While specific data were not disclosed, Gilead reported an "early trend in improvement" in overall survival, a key secondary endpoint. The safety profile of the combination therapy was consistent with previously established data for both drugs individually, with no new safety concerns identified.

Market Implications and Competitive Landscape

The positive results from the Ascent-04 trial could have significant implications for Trodelvy's market position. Analysts at Truist Securities suggest that approval for this combination in the first-line setting could "potentially double the addressable market" for Trodelvy in metastatic TNBC. Currently, Trodelvy is approved as a monotherapy for mTNBC patients who have undergone at least two prior lines of systemic therapies.

However, Trodelvy faces increasing competition in the TROP2-targeted ADC space. AstraZeneca and Daiichi Sankyo's Datroway recently entered the U.S. market, while Kelun-Biotech's sacituzumab tirumotecan (sac-TMT), partnered with Merck, has launched in China. Additionally, emerging PD-L1 combination therapies, particularly those incorporating VEGF blockers, may present future competition.

Despite these challenges, Citi analysts maintain a bullish outlook on Trodelvy's potential, predicting peak sales of $3.2 billion by 2030, surpassing the consensus estimate of $2.9 billion. Gilead estimates that the addressable patient population for the Ascent-04 trial could reach approximately 10,000 across the U.S. and EU5 countries by 2030.

As Gilead prepares to discuss these results with regulatory authorities, the company continues to explore Trodelvy's potential in other settings. Ongoing trials include Ascent-03, evaluating Trodelvy against chemotherapy in first-line, PD-L1-negative metastatic TNBC, and Ascent-05, investigating Trodelvy and chemotherapy as an adjuvant treatment for TNBC patients with residual invasive disease after surgery and neoadjuvant therapy.