Abstract PS1-13-24: Safety analysis of ASCENT-03, a phase 3 study of sacituzumab govitecan (SG) vs chemotherapy (chemo) for previously untreated advanced triple-negative breast cancer (TNBC) in patients (pts) who are not candidates for PD-(L)1 inhibi

Abstract Background: In ASCENT-03 SG demonstrated statistically significant and clinically meaningful improvement in progression-free survival versus chemo for pts with previously untreated, locally advanced unresectable or metastatic TNBC who were not candidates for PD-(L)1i. We report the first in-depth safety analysis. Methods: Pts were randomized 1:1 to SG (10 mg/kg IV days 1 and 8 per 21-day cycle) or chemo (taxane or gemcitabine + carboplatin [G+C]) until disease progression or unacceptable toxicity. Exposure-adjusted incidence rates (EAIRs; number of pts with ≥ 1 specific treatment-emergent adverse event [TEAE] per pt-year of exposure) were measured in an exploratory analysis. Incidence, severity, time to onset, duration, and impact of supportive care measures for select TEAEs were assessed. Results: The safety set included 551 pts who received ≥1 dose of study drug (SG: 275; chemo: 276, 44% gemcitabine + carboplatin, 56% taxane). Pts received SG for median 8.3 months, taxane for 6.3 months, and G+C for 5.8 months. EAIRs, incidence, and time to onset/duration of specified TEAEs are shown in the Table. Grade ≥ 3 TEAEs occurred in 66% and 62% of pts treated with SG and chemo, respectively. The most common TEAEs with SG were neutropenia (68%), nausea (61%), and alopecia (55%) and with chemo were neutropenia (57%), anemia (50%), and fatigue (47%). Any-grade/grade ≥ 3 neutropenia was reported in 68%/45% of pts with SG and 57%/41% with chemo. EAIR of neutropenia was comparable between treatment groups. Neutropenia leading to dose reduction occurred in 20% of pts in both groups; 1 case in the SG group and 3 in the chemo group led to treatment discontinuation. Granulocyte-colony stimulating factor (G-CSF) was used at any time in 59% and 38% of patients and as primary prophylaxis in 20% and 10% pts in the SG and chemo groups, respectively. Any-grade/grade ≥ 3 diarrhea was reported in 54%/9% of pts with SG and 20%/1% with chemo. EAIR of diarrhea was higher in the SG group than the chemo group. Diarrhea leading to dose reduction occurred in 5% of pts in the SG group and 1% in the chemo group; 1 case in the SG group led to treatment discontinuation. Antidiarrheal treatment was given to 72% of pts who experienced diarrhea in the SG group and 44% in the chemo group. Conclusions: In pts with previously untreated advanced TNBC who were not candidates for PD-(L)1i, the SG group had a similar rate of grade ≥ 3 TEAEs and lower rates of TEAEs leading to dose reduction and discontinuation. Accounting for the longer duration of treatment with SG, EAIR of neutropenia was similar between treatment groups, while diarrhea remained higher with SG. It is important to manage these AEs proactively according to established guidelines. Taken together, the overall safety profile was consistent with the known safety profile for SG. Citation Format: S. Hurvitz, A. Bardia, S. M. Tolaney, K. Punie, C. Barrios, A. Schneeweiss, R. Hegg, E. Tokunaga, J. Sohn, S. Kim, S. Im, Y. Park, B. Rapoport, D. Motola, D. A. Yardley, F. Dalenc, M. Oliveira, B. Pistilli, G. Vidal, S. Paluch-Shimon, B. Xu, T. Valdez, D. Zhang, S. Padman, J. Cortés. Safety analysis of ASCENT-03, a phase 3 study of sacituzumab govitecan (SG) vs chemotherapy (chemo) for previously untreated advanced triple-negative breast cancer (TNBC) in patients (pts) who are not candidates for PD-(L)1 inhibitors (PD-[L]1i) [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS1-13-24.