Trodelvy-Keytruda combo successful in Phase 3 breast cancer trial

Gilead has announced a significant advancement in the treatment of an aggressive type of breast cancer through its Phase 3 study named ASCENT-04. The study focuses on the combination of Gilead’s antibody-drug conjugate Trodelvy with Merck’s Keytruda to treat patients suffering from inoperable locally advanced or metastatic triple-negative breast cancer. A critical aspect of this patient group is that their tumors express PD-L1, a protein associated with the immune checkpoint system, which is targeted by Keytruda.

This development marks a success for Trodelvy, particularly following a series of setbacks experienced in the previous year. The company has confirmed that the study has achieved its primary endpoint of progression-free survival, though detailed numerical data is currently missing from the announcement. Gilead has committed to presenting these detailed results at an upcoming medical meeting. Additionally, the company intends to engage with regulatory bodies to discuss the study outcomes, although no specific timelines for marketing application submissions have been disclosed.

The study also explored another crucial endpoint, overall survival. Although this data remains immature at the time of the initial analysis, Gilead has indicated an "early trend" suggesting improved survival rates for patients treated with the Trodelvy and Keytruda combination. Importantly, the safety profile of the combination aligns with what is already known about the individual agents, according to Gilead.

Trodelvy, which directs its action towards TROP2, is currently authorized for use as a third-line treatment in metastatic triple-negative breast cancer and as a fourth-line treatment for HR+/HER2- breast cancer. Gilead is actively working to broaden the application of Trodelvy in both breast cancer and other cancer types, though these efforts have faced obstacles. For instance, last year, Gilead withdrew Trodelvy’s accelerated approval label for bladder cancer after a study failed to demonstrate survival benefits. Moreover, in 2024, Trodelvy did not succeed in a critical lung cancer study.

Gilead's ongoing research includes testing the combination of Trodelvy and Keytruda for post-surgical treatment of triple-negative breast cancer, as well as exploring its application in a type of lung cancer. Trodelvy is also being evaluated as a standalone treatment against chemotherapy in patients with metastatic triple-negative breast cancer who are not suitable candidates for immune checkpoint drugs. The results of this Phase 3 trial are anticipated in the near future.

In a related development in January, Daiichi Sankyo and AstraZeneca secured approval for their TROP2-directed antibody-drug conjugate, Datroway, for a type of breast cancer. This approval came despite mixed results in clinical trials, highlighting the competitive and challenging landscape of developing treatments for aggressive cancers like triple-negative breast cancer.

Overall, the findings from the ASCENT-04 study provide a glimmer of hope for advancements in treating a particularly challenging form of breast cancer, offering potential new therapeutic avenues for patients who have limited options. The medical community eagerly anticipates the detailed data and further regulatory discussions that could expand the use of Trodelvy in cancer treatment.