NEW YORK – Gilead Sciences on Monday said it will share with regulators that its Trop-02-directed antibody-drug conjugate Trodelvy (sacituzumab govitecan-hziy) combined with Merck's checkpoint inhibitor Keytruda (pembrolizumab) benefited triple-negative breast cancer patients with PD-L1-expressing tumors.
Gilead said its Phase III ASCENT-04 trial showed that treatment with Trodelvy-Keytruda led to statistically significant and clinically meaningful improvements in progression-free survival in patients with inoperable, locally advanced or metastatic PD-L1-positive TNBC compared to Keytruda and chemotherapy. PD-L1-positivity in this setting is defined as a PD-L1 combined positive score of at least 10 based on immunohistochemistry testing.
Researchers will continue to monitor the treatment's effect on overall survival, which is still too soon to determine, although Gilead indicated there was an early trend showing that those on Trodelvy-Keytruda are living longer than those in the comparator arm.
AstraZeneca and Daiichi Sankyo's Enhertu (trastuzumab deruxtecan), another ADC available on the market, treats individuals with low or ultralow HER2 expression, which based on current HER2 testing parameters, would include some TNBC patients. According to Foster City, California-based Gilead, however, the ASCENT-04 study uniquely tested an ADC with immunotherapy in aggressive breast cancers.
"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," said Gilead Chief Medical Officer Dietmar Berger in a statement. "For patients with this difficult-to-treat type of breast cancer, these results potentially offer a new pathway that may redefine their treatment options."
Sara Tolaney, chief of the breast oncology division at Dana-Farber Cancer Institute and the primary investigator of the study, said this new combination approach will improve patient outcomes.
"For patients with metastatic triple-negative breast cancer, there is a critical need for more effective treatment options," she said in a statement.
The ASCENT-04/KEYNOTE-D19 study, which began in 2022 and includes 443 patients, is one of several Phase III trials, in which researchers are investigating Trodelvy. Investigators are also evaluating it in other metastatic breast cancers, as well as in lung and gynecological cancers. On its own, Trodelvy is approved for metastatic TNBC patients who have received prior treatment. Gilead said in February that sales for the drug, which it called the "standard of care" for second-line metastatic TNBC, climbed 24 percent from 2023 to 2024.
Keytruda, meanwhile, is an immunotherapy used to treat 18 types of cancer, including TNBC. In patients with TNBC, doctors can prescribe it with chemotherapy either before surgery, or for inoperable or advanced PD-L1-positive TNBC.
In addition to discussing the ASCENT-04 data with regulators, Gilead said it plans to present the findings at a future medical meeting.