ASCENT-03 achieved its primary endpoint of superior PFS with Trodelvy (sacituzumab govitecan-hziy) plus pembrolizumab versus chemotherapy plus pembrolizumab in first-line mTNBC, marking a pivotal advancement for this antibody-drug conjugate in an earlier treatment setting. The highly statistically significant results, coupled with a manageable safety profile consistent with known profiles of both agents, support regulatory submissions and potential expansion of Trodelvy’s label beyond second-line mTNBC. This data could establish a new standard of care for first-line mTNBC treatment if approved.
Drug Profile & Mechanism
- Trodelvy (sacituzumab govitecan-hziy) is a first-in-class Trop-2-directed antibody-drug conjugate (ADC) comprising an anti-Trop-2 antibody coupled to SN-38, a topoisomerase I inhibitor
- Trop-2 is highly expressed across multiple epithelial cancers, including triple-negative breast cancer, making it an attractive therapeutic target
- Pembrolizumab is an anti-PD-1 immune checkpoint inhibitor that enhances T-cell-mediated antitumor immunity
- The combination rationale leverages immunogenic cell death induced by chemotherapy with immune checkpoint blockade to potentially enhance antitumor responses
- Patient population: first-line metastatic triple-negative breast cancer, regardless of PD-L1 status
- Trodelvy is currently approved for second-line mTNBC and metastatic urothelial cancer
Regulatory Milestone Details
- ASCENT-03 is a global, randomized, open-label Phase 3 trial comparing Trodelvy plus pembrolizumab versus investigator’s choice chemotherapy plus pembrolizumab
- Primary endpoint of progression-free survival was met with highly statistically significant improvement favoring the Trodelvy combination
- Secondary endpoints include overall survival (OS), objective response rate (ORR), duration of response (DoR), and safety—full data will be presented at an upcoming medical meeting
- Safety profile was consistent with the known profiles of both Trodelvy and pembrolizumab, with no new safety signals identified
- Study enrolled patients with previously untreated metastatic triple-negative breast cancer, regardless of PD-L1 expression status
- Supporting regulatory submissions expected in 2025 based on these pivotal results
Practice Implications
- If approved, Trodelvy plus pembrolizumab could become a preferred first-line regimen for metastatic triple-negative breast cancer, shifting current treatment paradigms
- The combination may offer improved efficacy over standard chemotherapy-immunotherapy doublets currently used in clinical practice
- Results may influence treatment sequencing decisions, as Trodelvy is currently used in second-line settings—earlier use could impact subsequent therapy options
- The PD-L1-agnostic enrollment may broaden the eligible patient population compared to current immunotherapy-based first-line regimens
- Oncologists should anticipate potential label expansion and prepare for integration of this combination into treatment algorithms pending full data presentation and regulatory review
Development Status & Next Steps
- Topline results announced October 2025; full efficacy and safety data to be presented at an upcoming major medical congress
- Regulatory submissions to FDA and international regulatory agencies planned for 2025
- Overall survival data remain immature and will continue to be monitored as a key secondary endpoint
- Additional analyses will include subgroup assessments (PD-L1 status, disease characteristics) and quality of life data
- If approved, launch timing would likely occur in 2026, pending regulatory review timelines
- Ongoing studies continue to evaluate Trodelvy in additional breast cancer settings and other solid tumors
