Anbenitamab plus albumin-bound docetaxel (nab-docetaxel) ± carboplatin (Cb) versus trastuzumab and pertuzumab plus docetaxel (THP) ± Cb as neoadjuvant therapy for HER2-positive early or locally advanced breast cancer: A randomized, open-label, multicenter, phase 3 trial.

Abstract

LBA660 Background: THP ± Cb represent the standard neoadjuvant treatment for HER2-positive breast cancer. Despite achieving total pathological complete response (tpCR) rates between 39.3% and 56.0%, there remains a clinical need to further improve outcomes, as tpCR is strongly correlated with long-term survival. Anbenitamab (KN026) is a novel biparatopic antibody targeting HER2 domains II and IV. This phase 3 study (NCT06747338) compared the efficacy and safety of an Anbenitamab-based regimen to the standard-of-care THP± Cb regimen in the neoadjuvant setting. Methods: Patients with HER2-positive early or locally advanced breast cancer were randomized 1:1 to receive 6 cycles of either Anbenitamab plus nab-docetaxel ± Cb [Anbenitamab arm] or trastuzumab, pertuzumab, and docetaxel ± Cb [THP ± Cb arm]. Randomization was stratified by clinical stage, hormone receptor status, and planned carboplatin use. The primary endpoint was tpCR (ypT0/is, ypN0) as assessed by a Blinded Independent Review Committee (BIRC). Results: A total of 521 patients were randomized. The study met its primary endpoint, with a significantly higher tpCR rate in Anbenitamab arm compared to THP ± Cb arm (62.4% [95% CI: 56.2–68.2] vs. 51.2% [95% CI: 44.9–57.4]). The stratified difference in tpCR was 11.4% (95% CI: 3.2–19.6); one-sided P = 0.0036). Consistent results were observed for investigator assessed tpCR (63.9% [95% CI: 57.8–69.7] vs. 51.2% [95% CI: 44.9–57.4], one-sided P = 0.0011). Similar improvements in BIRC-tpCR were observed across all prespecified subgroups, including those defined by hormone receptor status, clinical stage, and planned carboplatin use. BIRC-assessed breast pCR was also significantly higher in Anbenitamab arm (64.6% vs 55.0%, one-sided P = 0.0099). The overall incidence of treatment emergent adverse events (TEAEs) was 98.5% in Anbenitamab arm versus 98.8% in THP ± Cb arm. Grade ≥3 TEAE rates were similar (29.3% vs 28.3%). Most common Grade ≥3 TEAEs were neutropenia (11.4 % vs 10.9%) and leukopenia (7.6% vs 8.5%). TEAEs leading to interruption of any study drug occurred in 5.7% vs 7.4% of patients. Permanent discontinuations due to TEAEs occurred in 4.9% vs 3.5% of patients. Safety profiles were primarily hematologic and gastrointestinal toxicities， consistent with known safety profiles of respective single agents, and no new safety signal was observed. Conclusions: Anbenitamab plus nab-docetaxel ± Cb significantly improved tpCR rate compared with standard of care as neoadjuvant therapy in patients with early or locally advanced HER2-positive breast cancer, with a manageable safety profile. These results support Anbenitamab-based regimen as a potential new standard of care. Clinical trial information: NCT06747338 .