Trodelvy (sacituzumab govitecan) plus Keytruda (pembrolizumab) demonstrates a clinically meaningful improvement in progression free survival in patients with previously untreated PD-L1+ metastatic triple-negative breast cancer- Gilead Sciences

Gilead Sciences Inc. announced positive topline results from the Phase III ASCENT-04/KEYNOTE-D19 study, demonstrating that Trodelvy (sacituzumab govitecan-hziy) plus Keytruda (pembrolizumab) significantly improved progression-free survival (PFS) compared to Keytruda and chemotherapy in patients with inoperable (unresectable) locally advanced or metastatic triple-negative breast cancer (mTNBC) whose tumors express PD-L1 (CPS ≥ 10). The study met its primary endpoint, showing a statistically significant and clinically meaningful improvement in PFS.

About the ASCENT-04/KEYNOTE-D19 Study

In 2021, Gilead entered a collaboration with Merck & Co. to investigate sacituzumab govitecan in combination with pembrolizumab in the Phase III trial, ASCENT-04/KEYNOTE-D19. The ASCENT-04/KEYNOTE-D19 study ( NCT05382286) is a global, open-label, randomized Phase III trial evaluating the efficacy and safety of sacituzumab govitecan in combination with pembrolizumab compared with treatment of chemotherapy plus pembrolizumab in patients with previously untreated, inoperable locally advanced or metastatic triple-negative breast cancer (TNBC) whose tumors express PD-L1. The study enrolled 443 patients across multiple study sites.

Patients were randomized in a 1:1 ratio to receive either sacituzumab govitecan (10 mg/kg intravenously on Days 1 and 8 of a 21-day cycle) plus pembrolizumab (200 mg intravenously on Day 1 of a 21-day cycle) or chemotherapy plus pembrolizumab. The chemotherapy regimen included gemcitabine plus carboplatin, paclitaxel, or nab-paclitaxel. Treatment continued until blinded independent central review (BICR)-verified disease progression or unacceptable toxicity. Patients randomized to chemotherapy were allowed to crossover and receive sacituzumab govitecan upon disease progression.

The primary endpoint of the study is progression-free survival (PFS) as determined by BICR using RECIST v1.1. Secondary endpoints include overall survival (OS), objective response rate (ORR), duration of response (DOR), time to onset of response (TTR), patient-reported outcomes (PROs), and safety.

Overall survival (OS) is a key secondary endpoint and was not mature at the time of the PFS primary analysis. However, in the ASCENT-04 study, there was an early trend in improvement for OS with Trodelvy plus Keytruda. Gilead will continue to monitor OS outcomes, with ongoing patient follow-up and further analyses planned. The safety profile of Trodelvy plus Keytruda in the ASCENT-04 study was consistent with the known safety profile of each agent. No new safety signals were identified with the combination.

Detailed results from the study will be presented at a future medical meeting and discussed with regulatory authorities. The use of Trodelvy plus Keytruda in patients with previously untreated PD-L1+ metastatic TNBC is investigational, and the safety and efficacy of this use have not been established.

The significant and meaningful improvement in PFS demonstrated in ASCENT-04 further reinforces the potential of Trodelvy plus Keytruda as a much-needed new treatment option for patients with previously untreated inoperable (unresectable) PD-L1+ locally advanced or mTNBC.

"For patients with metastatic triple-negative breast cancer, there is a critical need for more effective treatment options,” said Dr. Sara Tolaney, Dana-Farber Cancer Institute and primary investigator of the ASCENT-04 study. “These data suggest that the combination of sacituzumab govitecan-hziy and pembrolizumab may offer a new treatment approach—bringing together a potent antibody drug conjugate with immunotherapy to improve outcomes for patients.”

"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 Dr. Dietmar Berger,  Chief Medical Officer, Gilead Sciences. “For patients with this difficult to treat type of breast cancer, these results potentially offer a new pathway that may redefine their treatment options.”