Gilead's Trodelvy-Keytruda Combo Succeeds in First-Line Triple-Negative Breast Cancer

In a significant development for breast cancer treatment, Gilead Sciences announced that its drug Trodelvy, in combination with Merck & Co.'s Keytruda, has shown promising results in treating first-line metastatic triple-negative breast cancer (TNBC) in patients with PD-L1-positive tumors. This breakthrough was reported from the phase 3 Ascent-04 trial, also known as Keynote-D19, which marked the first instance of a TROP2-targeted antibody-drug conjugate (ADC) proving superior when combined with an immunotherapy agent in this context.

The combination treatment of Trodelvy and Keytruda outperformed the existing standard of Keytruda plus chemotherapy in delaying cancer progression or death among patients who had not received prior treatment. The trial focused on patients with a PD-L1 positivity as defined by a combined positive score of at least 10, a criterion established when Keytruda and chemotherapy were approved by the FDA for this indication in 2020.

Dietmar Berger, Gilead's chief medical officer, emphasized the transformative potential of this treatment combination in early intervention for metastatic breast cancer, marking a substantial advancement in the field. This success arrives at a critical time for Trodelvy, which has faced increasing competition from other TROP2 ADCs like AstraZeneca and Daiichi Sankyo’s Datroway in the U.S. and Kelun-Biotech’s sacituzumab tirumotecan in China.

Trodelvy's journey has not been without challenges. It has experienced setbacks, including a notable failure in treating previously treated non-small cell lung cancer and a phase 3 trial failure that resulted in the withdrawal of accelerated approval for a bladder cancer indication. Despite these hurdles, the Ascent-04 trial's results underscore a "significant and meaningful" improvement in progression-free survival among the trial participants, strengthening Gilead’s belief in the potential of Trodelvy and Keytruda as a vital new treatment for PD-L1-positive metastatic TNBC.

While the data on overall survival is still immature, initial observations suggest a potential improvement with the Trodelvy-Keytruda combination. Gilead plans to engage with regulatory authorities to discuss these findings. Despite existing treatment options, more than half of the PD-L1-positive TNBC patients do not progress to second-line treatments, highlighting the need for more effective first-line therapies.

Analysts at Citi have highlighted the market potential for Trodelvy, projecting a peak sales figure of $3.2 billion by 2030, surpassing the consensus estimate of $2.9 billion. Gilead sees the addressable patient population for Ascent-04 at around 10,000 patients across the U.S. and major European countries by 2030.

Beyond the Ascent-04 trial, Gilead anticipates results from other ongoing studies, including the Ascent-03 trial, which is comparing Trodelvy to chemotherapy in PD-L1-negative metastatic TNBC patients, and the Ascent-05 study, which is evaluating Trodelvy and chemotherapy as an adjuvant treatment for TNBC patients with residual invasive disease post-surgery.

Trodelvy was initially a central component of Gilead's oncology strategy. However, following several clinical setbacks, investor focus has shifted back to Gilead's core HIV business, particularly the potential launch of lenacapavir, a biannual PrEP drug, and the development of anito-cel, a CD19 CAR-T candidate in collaboration with Arcellx.