Abstract PS4-06-17: First clinical data of DB-1310 (HER3-targeted antibody-drug-conjugate), in patients with pretreated hormone receptor-positive/HER2-negative breast cancer: efficacy and safety data from a phase 1/2a trial

Abstract Background: HER3-targeted antibody-drug conjugates (ADCs) have shown benefits in breast cancer (BC). DB-1310 is a novel ADC comprised of a humanized anti-HER3 IgG1 monoclonal antibody with a highly internalizing unique Domain I epitope, a cleavable peptide linker, and a potent DNA topoisomerase I inhibitor P1021. Initial clinical data demonstrated a manageable safety profile and encouraging anti-tumor activity, particularly in patients with EGFR-mutant NSCLC (Lisberg ASCO 2025). Here, we present the efficacy and safety results of DB-1310 in pretreated hormone receptor-positive (HR+), HER2-negative (HER2-) BC patients. Methods: In the Phase 1 part of this trial (NCT05785741), patients with advanced solid tumors, including HR+/HER2- BC, received DB-1310 monotherapy intravenously every three weeks (Q3W). Safety was the primary endpoint, with efficacy endpoints including objective response rate (ORR), duration of response (DoR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) as secondary endpoints. Results: As of July 04, 2025, a total of 207 patients with solid tumors were enrolled and treated with DB-1310 monotherapy (1.5-6.5 mg/kg, Q3W) in Phase 1 (ECOG PS 1, 84.1%; White, 26.1%; Asian, 69.1%). Among these, 16 HR+/HER2- BC patients were enrolled (3.0-5.5 mg/kg, Q3W), with 15 of them being efficacy-evaluable, and a median prior line of systemic therapy was 2 (range, 1-7). Efficacy Results (N=15 HR+/HER2- BC patients from Phase 1): nine achieved a partial response (one pending confirmation), and four achieved stable disease, resulting in a confirmed ORR of 53.3% (95%CI: 26.59, 78.73) and a DCR of 86.7% (95%CI: 59.54, 98.34). Notably, all partial responses occurred in patients treated with 5-5.5 mg/kg (N=13), yielding an unconfirmed ORR of 69.2%, a confirmed ORR of 61.5%, and a DCR of 92.3% for this dose range. The median DoR is not reached. Median PFS is 14.78 months (95% CI: 11.60, not evaluable) and median OS is 14.69 months (95% CI: 11.89, not evaluable). Safety Results (N=207, all enrolled patients from Phase 1): The safety profile was assessed in the entire Phase 1 part. Treatment-related adverse events (TRAEs) of Grade (G) ≥ 3 occurred in 89 (43.0%) patients, and 25 patients (12.1%) had treatment-related serious adverse events. TRAEs led to dose reduction in 38 (18.4%) and discontinuation in 9 (4.3%) patients. No TRAE-related deaths were reported. Most common TRAEs (any grade/≥G3; >20% overall) were neutrophile count decreased (49.3%/ 26.1%), anemia (47.8%/ 6.8%), platelet count decreased (45.4%/ 15.9%), white blood cell count decreased (43.5%/ 11.1%), nausea (40.6%/ 1.0%), decreased appetite (29.5%/ 0.5%), aspartate aminotransferase increased (26.6%/ 0), alopecia (26.1%/ 0), vomiting (24.6%/ 0), and hypoalbuminemia (21.7%/ 0). Interstitial lung disease/pneumonitis occurred in 10 pts (4.8%; one Grade 2, all others G1). The safety profile in the 16 HR+/HER- BC patients was consistent with the overall Phase 1 part. Conclusion: DB-1310 showed promising anti-tumor activity in heavily pretreated HR+/HER2- BC patients. The manageable safety profile observed in the larger Phase 1 part, involving 207 patients, is consistent with that of the BC subpopulation, supporting its further development. Citation Format: Y. Yin, A. Spira, H. Lan, M. Zhao, Y. Mao, W. Yao, Y. Sun, J. Wu, X. Sun, S. Liu, H. Mu, K. Wang, Y. Qiu, E. Hamilton. First clinical data of DB-1310 (HER3-targeted antibody-drug-conjugate), in patients with pretreated hormone receptor-positive/HER2-negative breast cancer: efficacy and safety data from a phase 1/2a 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 PS4-06-17.