ASCENT-03: Efficacy by biomarker subgroup with sacituzumab govitecan (SG) vs chemotherapy (chemo) in participants (pts) with previously untreated advanced triple-negative breast cancer (TNBC) who are not candidates for PD-(L)1 inhibitors (PD-[L]1i).
Year: 2026
Type: conference-abstract
Abstract: 1014 Background: SG demonstrated significant and clinically meaningful progression-free survival (PFS) improvement vs chemo in pts with previously untreated, locally advanced unresectable or metastatic TNBC who were not candidates for PD-(L)1i in ASCENT-03 (NCT05382299). We report preplanned exploratory efficacy analyses in ASCENT-03 by Trop-2 expression, BRCA status, and HER2 expression. Methods: 588 pts randomized 1:1 to SG or chemo (taxane or gemcitabine + carboplatin). Trop-2 expression was measured by immunohistochemistry (IHC), tumor BRCA (tBRCA) status by whole exome sequencing, and HER2 expression by in situ hybridization (ISH) and IHC, all in centrally tested tumor samples (fresh or archival; 43% from metastatic sites). Pts were subgrouped by Trop-2 expression quartile, tBRCA wild-type (WT) or mutant (mut; mut in BRCA1, BRCA2, or both) status, and HER2 status (IHC 0 vs Low [IHC 1+ or IHC 2+/ISH-]). Biomarker status was analyzed to determine association with PFS by blinded independent central review (BICR). Other efficacy outcomes by biomarker status will be presented. Results: Median Trop-2 H-score: 240; H-scores by quartile (Q): Q1 0-184, Q2 185-239, Q3 240-283, Q4 284-300. Trop-2 expression was available in 499 pts. PFS by BICR was longer with SG vs chemo in all Trop-2 expression quartiles (Table). Hazard ratio (HR; 95% confidence interval [CI]) was 0.54 (0.35-0.84) in Q1, 0.62 (0.40-0.97) in Q2, 0.84 (0.54-1.31) in Q3, and 0.60 (0.38-0.95) in Q4. tBRCA status was available in 423 pts; proportion of pts with tBRCA mutations was comparable between treatment groups (~18%). PFS was longer with SG vs chemo in tBRCA WT and mut subgroups, with HR (95% CI) 0.70 (0.54-0.92) in tBRCA WT and 0.59 (0.32-1.09) in tBRCA mut. HER2 status was available in 551 pts; PFS was longer with SG vs chemo in both HER2 subgroups. HR was 0.63 (0.46-0.85) in the IHC 0 subgroup and 0.74 (0.55-1.01) in the HER2 Low subgroup. Conclusions: PFS was longer with SG vs chemo across all Trop-2 categories, tBRCA genotypes, and HER2 subgroups. These results reinforce the significant, clinically meaningful benefit of SG as first-line treatment for pts in this population across multiple biomarker subgroups. Clinical trial information: NCT05382299 . Efficacy, BICR N Median PFS (95% CI), months Biomarker Subgroup SG Chemo SG Chemo HR (95% CI) Trop-2(n = 499) Q1 68 55 8.5(5.6-12.7) 5.5(4.2-8.1) 0.54(0.35-0.84) Q2 60 62 8.3(5.6-12.4) 6.8(4.2-9.0) 0.62(0.40-0.97) Q3 50 74 9.7(7.6-11.3) 7.0(5.3-8.5) 0.84(0.54-1.31) Q4 74 56 9.9(6.9-NR) 8.1(4.4-8.5) 0.60(0.38-0.95) tBRCA(n = 423) WT 177 169 8.8(7.2-9.9) 6.9(5.4-8.3) 0.70(0.54-0.92) Mut 40 37 12.7(7.2-18.7) 8.3(5.6-11.2) 0.59(0.32-1.09) HER2(n = 551) IHC 0 115 138 8.3(6.9-10.3) 5.6(4.3-7.0) 0.63(0.46-0.85) Low
Source: Journal of Clinical Oncology
Authors: Carlos H. Barrios, Sara A. Hurvitz, Sara M. Tolaney, Javier Cortes, Kevin Punie, Andreas Schneeweiss, Adam Brufsky, Mafalda Oliveira, Joohyuk Sohn, Eriko Tokunaga, Alessandra Fabi, Yeon Hee Park, Binghe Xu, Roberto Hegg, Meghna Das Thakur, Yajia Zhang, Natalya Vaksman, Catherine Lai, Aditya Bardia
Institutions: Latin American Cooperative Oncology Group (LACOG), University of Washington, Fred Hutch Cancer Center, Harvard University, Dana-Farber Cancer Institute, Ziekenhuis aan de Stroom, German Cancer Research Center, University Hospital Heidelberg, Magee-Womens Hospital, UPMC Hillman Cancer Center, University of Pittsburgh Medical Center, Vall d'Hebron Hospital Universitari, Vall d'Hebron Institute of Oncology, Yonsei Cancer Hospital, National Hospital Organization Kyushu Cancer Center, Università Cattolica del Sacro Cuore, Agostino Gemelli University Polyclinic, Istituti di Ricovero e Cura a Carattere Scientifico, Samsung Medical Center, Sungkyunkwan University, Chinese Academy of Medical Sciences & Peking Union Medical College, Cancer Hospital of Chinese Academy of Medical Sciences, Universidade de São Paulo, Gilead Sciences (United States), University of California, Los Angeles, UCLA Jonsson Comprehensive Cancer Center
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: bronze
OpenAlex ID: W7162526259