Key Points

Question  Does the combination of ERBB2-biparatopic antibody (anbenitamab) and albumin-bound docetaxel (HB1801) increase the total pathological complete response (tpCR) rate compared with the standard regimen of trastuzumab, pertuzumab, and docetaxel in patients with ERBB2-positive breast cancer?

Findings  In this randomized clinical trial that included 521 patients with early or locally advanced ERBB2-positive breast cancer, the tpCR rate was significantly higher in the anbenitamab and HB1801 group compared with the control group; both regimens had manageable safety profiles.

Meaning  These findings suggest that neoadjuvant anbenitamab and HB1801 led to clinically meaningful tpCR improvement; this new combination might establish a new standard for neoadjuvant treatment in ERBB2-positive breast cancer.

Abstract
 Neoadjuvant Anbenitamab and HB1801 in ERBB2-Positive Breast Cancer
Visual Abstract.

IMPORTANCE  The combination of neoadjuvant taxanes with trastuzumab and pertuzumab remains the cornerstone treatment strategy in ERBB2-positive breast cancer. Anbenitamab (a ERBB2-biparatopic antibody that induces profound receptor clustering) and HB1801 (a solvent-free albumin-bound docetaxel), have shown promising antitumor activity and an acceptable safety profile in patients with breast cancer.

OBJECTIVE  To evaluate whether neoadjuvant anbenitamab combined with HB1801 could improve efficacy without increasing toxic effects for patients with early ERBB2-positive breast cancer.

DESIGN, SETTING, AND PARTICIPANTS  This multicenter, phase 3 registrational randomized clinical trial enrolled patients with stage II or III ERBB2-positive breast cancer from 61 hospitals in China between December 19, 2024, and August 29, 2025 (data cutoff: January 28, 2026). Data were analyzed from February 1 to March 20, 2026.

INTERVENTIONS  Patients were randomly assigned (1:1) to receive 6 cycles of neoadjuvant anbenitamab plus HB1801, with or without carboplatin (investigational group), or trastuzumab, pertuzumab, and docetaxel, with or without carboplatin (control group).

MAIN OUTCOMES AND MEASURES  The primary end point was total pathological complete response (tpCR) assessed by a blinded independent review committee.

RESULTS  Among 521 included patients (median age, 52.0 [23-79] years), 263 were randomized to the investigational group and 258 to the control group. The tpCR rate was significantly higher in the investigational group than the control group (164 patients [62.4%] vs 132 patients [51.2%]; absolute difference, 11.4 [95% CI, 3.2 to 19.6] percentage points; P = .004). Benefit was consistent across subgroups, including subgroups with hormone receptor–positive disease (77 patients [51.7%] vs 63 patients [44.4%]), hormone receptor–negative disease (87 patients [76.3%] vs 69 patients [59.5%]), early-stage disease (111 patients [63.8%] vs 87 patients [51.8%]), locally advanced disease (53 patients [59.6%] vs 45 patients [50.0%]), with carboplatin treatment (74 patients [66.7%] vs 61 patients [54.5%]), and without carboplatin treatment (90 patients [59.2%] vs 71 patients [48.6%]). Grade 3 or 4 treatment-related adverse events occurred in 77 patients (29.3%) in the investigational group and 73 patients (28.3%) of the control group. No treatment-related deaths occurred.

CONCLUSIONS AND RELEVANCE  This randomized clinical trial found that neoadjuvant anbenitamab and HB1801 in patients with breast cancer significantly improved the tpCR rate compared with standard therapy with a highly manageable safety profile. This new combination may offer an improved treatment option, although long-term survival follow-up analyses are warranted.

Trial Registration  ClinicalTrials.gov Identifier: NCT06747338