Primary Results From ASCENT-03: A Randomized Phase 3 Study of Sacituzumab Govitecan (SG) vs Chemotherapy (Chemo) in Patients (pts) With Previously Untreated Advanced Triple-Negative Breast Cancer (TNBC) Who Are Unable to Receive PD-(L)1 Inhibitors (PD-(L)1)

Background: Sacituzumab Govitecan (SG) has demonstrated PFS benefit in pretreated mTNBC (ASCENT) and in combination with pembrolizumab in 1L PD-L1+mTNBC (ASCENT-04). Here we report results from the phase 3 ASCENT-03 study (NCT05382299) of 1L SG vs chemotherapy (chemo) in patients with locally advanced unresectable or mTNBC who cannot receive a PD-(L)1 inhibitor. Methods: Patients with PD-L1−mTNBC (CPS<10) or PD-L1+mTNBC (CPS≥10) ineligible for PD-(L)1 inhibitor were randomized 1:1 to SG or chemo (paclitaxel, nab-paclitaxel, or gemcitabine+carboplatin). Primary end point was PFS by BICR. Key secondary end points included overall survival (OS), ORR and DOR by BICR, and safety. Results: 558 patients (279 per group) were randomized. SG showed a significant improvement in median PFS vs chemo (9.7 vs 6.9 mo). ORR: 48,4% for SG vs 45,5% for chemo. Median DOR was 12.2 mo vs 7.2 mo. OS data were immature. Any grade treatment-emergent adverse events (TEAEs) occurred in 99% of SG and 97% of chemo patients. TEAEs led to dose reductions in 37% (101) vs 45% (124) and treatment discontinuations in 4% (10) vs 12% (33), respectively. The most frequent grade≥3 TEAEs were neutropenia (43%) and diarrhea (9%) with SG and neutropenia (41%) and anemia (16%) with chemo. Conclusions: SG demonstrated a statistically significant and clinically meaningful PFS benefit and more durable responses vs chemo in 1L mTNBC. The safety profile of SG was manageable. This supports SG as potential new 1L standard for patients who are unable to receive a PD-(L)1i. Quellenangabe für Zweitpublikation : ESMO conference 2025, Javier Cortes et al, LBA 20 Publication History Article published online: 19 May 2026 © 2026. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany