Neoadjuvant Anbenitamab Combination Improves pCR in ERBB2+ Breast Cancer

Neoadjuvant treatment with anbenitamab plus HB1801 significantly improved total pathological complete response (tpCR) compared with trastuzumab (Herceptin), pertuzumab (Perjeta), and docetaxel in patients with stage II or III ERBB2-positive breast cancer, according to findings from a phase 3 trial published in JAMA Oncology.¹

At the January 28, 2026 data cut off, among 521 randomized patients, tpCR as assessed by a blinded independent review committee was achieved in 164 of 263 patients (62.4%) who received anbenitamab plus HB1801 compared with 132 of 258 patients (51.2%) who received the control treatment, an absolute difference of 11.4 percentage points (95% CI, 3.2-19.6; P =.004). The overall response rates were 94.3% and 92.2%, respectively, while breast pCR rates were 65.8% and 55.4%.

The efficacy benefit was observed across prespecified clinical subgroups. Among patients with hormone receptor–positive (HR+) disease, tpCR occurred in 51.7% of those receiving anbenitamab plus HB1801 compared with 44.4% with standard therapy. In HR–negative (HR–) disease, the corresponding rates were 76.3% and 59.5%. Patients with early-stage disease had tpCR rates of 63.8% and 51.8%, respectively, whereas those with locally advanced disease had rates of 59.6% and 50.0%.

Safety Findings

The safety profiles of the 2 regimens were comparable. Grade 3 or 4 treatment-related adverse events (TRAEs) occurred in 77 of 263 patients (29.3%) in the investigational group and 73 of 258 patients (28.3%) in the control group, with no treatment-related deaths in either arm. The most common grade 3 or grade 4 TRAEs in the investigational group were neutropenia, leukopenia, and anemia.

Nonhematologic adverse events—including rash, diarrhea, nausea, peripheral edema, and peripheral sensory neuropathy—were reported more frequently with anbenitamab plus HB1801, though most were grade 1 or 2. No dose reductions of anbenitamab were required, and no symptomatic left ventricular systolic dysfunction was observed in either arm.

Neo-Healer Trial: Design and Patient Characteristics

The multicenter, registrational phase 3 Neo-Healer trial (NCT06747338) enrolled patients with stage II or III ERBB2-positive breast cancer at 61 hospitals in China between December 19, 2024, and August 29, 2025.² A total of 521 patients were randomly assigned 1:1 to receive 6 cycles of either anbenitamab plus HB1801, or trastuzumab, pertuzumab, and docetaxel. Both regimens were administered with or without carboplatin at investigator discretion. The primary end point was tpCR assessed by a blinded independent review committee.

Among the 521 patients, 263 received the investigational regimen and 258 received the control regimen. The median age was 52 years in both groups. Overall, 55.9% of patients had HR+ disease, while 44.1% had HR– disease. Locally advanced disease was present in 34.4% of patients, and 42.8% received carboplatin. Most patients had ERBB2 IHC 3-positive disease, accounting for 88.7% of the overall population.

Anbenitamab Combo Advances as a Neoadjuvant Strategy

Anbenitamab is an ERBB2-biparatopic antibody designed to bind 2 nonoverlapping epitopes on the ERBB2 receptor simultaneously. Its mechanism of action is intended to promote receptor clustering, internalization, and lysosomal degradation, resulting in suppression of downstream signaling. HB1801 is an albumin-bound formulation of docetaxel that does not contain the solvents polysorbate 80 and ethanol used in conventional docetaxel formulations.

The study authors acknowledged that because anbenitamab and HB1801 were evaluated together, the trial cannot determine how much each individual agent contributed to the observed improvement in pCR. Nonetheless, the findings provide early phase 3 evidence supporting further evaluation of an alternative neoadjuvant treatment option for ERBB2-positive breast cancer. Longer follow-up would be needed to determine whether the improvement in tpCR translates into improved long-term clinical outcomes.

“This new combination may offer an improved treatment option, although long-term survival follow-up analyses are warranted,” study authors Li et al wrote.

REFERENCES

1. Li J, Liu T, Yu K Da, et al. Neoadjuvant Anbenitamab and HB1801 in ERBB2 -Positive Breast Cancer. JAMA Oncology. Published online September 3, 2026. doi:10.1001/jamaoncol.2026.3329

2. A Phase III Study of KN026 in Combination With HB1801 ± Carboplatin as Neoadjuvant Treatment for Early or Locally Advanced HER2-Positive Breast Cancer (Neo-Healer). ClinicalTrials.gov. Updated July 7, 2026. Accessed September 4, 2026. https://clinicaltrials.gov/study/NCT06747338