Abstract PS4-02-23: Biomarkers of response and resistance to Sacituzumab Govitecan in HR+/HER2− advanced breast cancer: interim results from the phase II SOLTI ACROSS-TROP2 Trial

Abstract Background: Sacituzumab Govitecan (SG) is an antibody-drug conjugate (ADC) containing a TROP2-directed antibody bound to a topoisomerase I inhibitor payload. SG is approved for the treatment of patients (pts) with metastatic triple-negative breast cancer who have received at least two prior systemic therapies, including one for advanced disease, and pts with hormone receptor-positive (HR+)/HER2-negative metastatic breast cancer (mBC) after endocrine therapy and ≥2 systemic treatments in the advanced setting. SG efficacy does not seem to correlate to TROP2 protein expression, and no additional efficacy biomarkers have been identified. Methods: SOLTI ACROSS-TROP2 (NCT06236269) is a phase II, open-label, single-arm trial investigating biomarkers of efficacy and mechanisms of resistance to SG in 100 pts with HR+/HER2- mBC who progressed during or after treatment with CDK4/6 inhibitors and received up to one prior chemotherapy or ADC regimen for metastatic disease. Pts received SG at 10 mg/kg via IV infusion on Days 1 and 8 of each 21-day cycle. Mandatory tumor biopsies were obtained at baseline and after 2-3 weeks of treatment (C2D1). The primary objective is to evaluate the change in CelTIL score (a composite score of tumor cellularity and tumor infiltrating lymphocytes) between baseline and C2D1 tumor samples (Nuciforo et al, Ann Oncol 2019). Key secondary endpoints include progression-free survival (PFS), overall response rate (ORR), and safety. Here we present the planned interim analysis results from the first 50 enrolled pts. Results: Between April and December 2024, 50 pts were enrolled. Median follow-up was 8.6 months (m). Median age was 58 (range 30-79), all pts were female, most were postmenopausal (78%), had no visceral metastases (64%), and received SG as second line for mBC after chemotherapy or ADC (70%). At data cut-off (May-25), 18/50 (36%) remained on treatment and 43/50 (86%) were evaluable for the primary endpoint. The mean increase in CelTIL score from baseline to C2D1 was 4.33 points (95% CI 0.99-7.65), indicating a significant overall change, with a greater and significant increase in patients that achieved radiological response (6.33 vs 3.13 points). PFS events occurred in 28/50 pts (maturity 56%). Median PFS was 6m (4.2-NR) both overall and among pts treated in second line for mBC. ORR was 37% and 38%, respectively. Grade ≥3 treatment-related adverse events (TRAEs) occurred in 48.0% of pts. Most common TRAEs were fatigue (58%), anemia (58%), neutropenia (54%), nausea (46%) and diarrhea (38%). Treatment discontinuation rate due to TRAEs was 8%. Conclusions: In this interim analysis of SOLTI ACROSS-TROP2, one cycle of SG led to an increase in CelTIL score, particularly among patients who achieved a radiological response. Consistent efficacy was observed in terms of PFS and ORR. The final results from the full cohort of 100 patients, along with a comprehensive translational analysis of paired pre- and on-treatment biopsies, are expected to provide further insights into biomarkers of response and mechanisms of resistance to SG in HR+/HER2- mBC. Citation Format: E. Ciruelos, T. Pascual, B. Adamo, M. Alva Bianchi, I. Blancas, L. Carnerero, R. Villanueva-Vázquez, B. Fullana, M. Melé, J. Salvador Bofill, J. M. Cejalvo, A. Ferrando-Díez, Y. Izarzugaza, M. Borrell, X. González Farré, G. Villacampa, M. Paes Dias, F. M. Juan, M. Oliveira. Biomarkers of response and resistance to Sacituzumab Govitecan in HR+/HER2− advanced breast cancer: interim results from the phase II SOLTI ACROSS-TROP2 Trial 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 PS4-02-23.