Why This Study Matters
Neoadjuvant taxane-based chemotherapy combined with trastuzumab and pertuzumab (THP) has long been the cornerstone regimen for early-stage ERBB2 (HER2)-positive breast cancer, but pathological complete response (pCR) rates with THP alone remain modest — historically around 50%–55% with 6 cycles — leaving room for improvement without adding toxicity. This phase 3 registrational trial tested whether pairing anbenitamab, a biparatopic ERBB2-targeted antibody engineered to induce dense receptor clustering and degradation, with HB1801, a solvent-free albumin-bound formulation of docetaxel, could raise response rates while preserving a manageable safety profile in patients with stage II or III disease.
Study Design
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). Patients were randomly assigned 1:1 to receive 6 cycles of neoadjuvant anbenitamab plus HB1801, with or without carboplatin (investigational group), or the standard regimen of trastuzumab, pertuzumab, and docetaxel, with or without carboplatin (control group). The primary end point was total pathological complete response (tpCR), assessed by a blinded independent review committee.
Patient Population
Among 521 included patients (median [IQR] age, 52.0 [23–79] years), 263 were randomized to the investigational group (anbenitamab + HB1801 ± carboplatin) and 258 to the control group (THP ± carboplatin). Baseline characteristics were well balanced between arms: 291 patients (55.9%) had hormone receptor (HR)-positive disease, 179 patients (34.4%) had locally advanced disease, and 223 patients (42.8%) received carboplatin. Patients who received carboplatin generally had a higher tumor burden, with 99 patients (44.4%) presenting with N2 or N3 disease. In the investigational group, 256 patients (97.3%) completed neoadjuvant treatment and 254 (96.6%) underwent surgery; in the control group, 255 patients (98.8%) completed treatment and underwent surgery.
Primary Endpoint Results
At the January 28, 2026, data cutoff, all 521 patients were evaluable for the primary analysis. Based on blinded independent review committee evaluation, tpCR was achieved in 164 of 263 patients (62.4%; 95% CI, 56.2%–68.2%) in the investigational group, compared with 132 of 258 patients (51.2%; 95% CI, 44.9%–57.4%) in the control group — an absolute difference of 11.4 percentage points (95% CI, 3.2 to 19.6; P = .004).
| Endpoint | Anbenitamab + HB1801 ± Cb | THP ± Cb |
|---|---|---|
| tpCR (primary endpoint) | 62.4% (164/263) | 51.2% (132/258) |
| Breast pCR | 65.8% | 55.4% |
| Overall response rate | 94.3% | 92.2% |
| tpCR, carboplatin recipients | 66.7% (74/111) | 54.5% (61/112) |
| tpCR, no carboplatin | 59.2% (90/152) | 48.6% (71/146) |
Subgroup Analyses
In prespecified exploratory subgroup analyses, the higher tpCR rate with anbenitamab plus HB1801 was generally consistent across subgroups, with one notable exception.
| Subgroup | Anbenitamab + HB1801 ± Cb (tpCR %) | THP ± Cb (tpCR %) | Absolute Difference (pts, 95% CI) |
|---|---|---|---|
| Intention-to-treat population | 62.4% (164/263) | 51.2% (132/258) | 11.2 (2.69–19.48) |
| ECOG performance status 0 | 63.9% (129/202) | 48.8% (103/211) | 15.0 (5.48–24.22) |
| ECOG performance status 1 | 57.6% (34/59) | 61.7% (29/47) | −4.1 (−21.89–14.42) |
| Hormone receptor–positive | 51.7% (77/149) | 44.4% (63/142) | 7.3 (−4.13–18.48) |
| Hormone receptor–negative | 76.3% (87/114) | 59.5% (69/116) | 16.8 (4.76–28.23) |
| Carboplatin: yes | 66.7% (74/111) | 54.5% (61/112) | 12.2 (−0.61–24.46) |
| Carboplatin: no | 59.2% (90/152) | 48.6% (71/146) | 10.6 (−0.72–21.52) |
The one subgroup that did not favor the investigational arm was patients with an ECOG performance status of 1, where the point estimate slightly favored the control group (57.6% vs 61.7%; absolute difference −4.1 points). The study authors attribute this to the subgroup's limited sample size rather than a true treatment-effect reversal.
Safety Profile
Rates of grade 3 or 4 treatment-related adverse events (TRAEs) were similar between arms overall: 77 of 263 patients (29.3%) in the investigational group versus 73 of 258 patients (28.3%) in the control group, with no treatment-related deaths and no symptomatic left ventricular systolic dysfunction reported in either arm. Nonhematologic adverse events — including rash, diarrhea, nausea, peripheral edema, and peripheral sensory neuropathy — were recorded more frequently in the investigational group. Grade 3 neutropenia occurred in 30 of 263 patients (11.4%) in the investigational group versus 28 of 258 patients (10.9%) in the control group. Treatment discontinuation occurred in 13 of 263 patients (4.9%) in the investigational group versus 9 of 258 patients (3.5%) in the control group.
| Adverse Event (any grade) | Anbenitamab + HB1801 ± Cb (n=263) | THP ± Cb (n=258) |
|---|---|---|
| Grade 3/4 TRAEs (any) | 29.3% (77/263) | 28.3% (73/258) |
| Grade 3 neutropenia | 11.4% (30/263) | 10.9% (28/258) |
| Diarrhea (any grade) | 54.4% | 45.3% |
| Nausea (any grade) | 34.2% | 21.3% |
| Peripheral sensory neuropathy (any grade) | 10.3% | 4.7% |
| Treatment discontinuation | 4.9% (13/263) | 3.5% (9/258) |
Interpretation and Broader Context
Anbenitamab's design allows it to bind two nonoverlapping epitopes on the ERBB2 receptor simultaneously — a biparatopic mechanism the study authors describe as forcing rapid receptor internalization and lysosomal degradation, distinct from the passive co-administration of separate monoclonal antibodies. HB1801's nanoparticle albumin-bound formulation eliminates the polysorbate 80 and ethanol solvents required for standard docetaxel, removing the need for high-dose glucocorticoid premedication.
"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."
— Study authors, "Meaning" statement, JAMA Oncology
The authors note that neoadjuvant TCbHP (the carboplatin-containing quadruplet) is currently recommended as a preferred standard in this setting, with pCR rates up to approximately 55% with 6 cycles, but at the cost of substantial hematologic, gastrointestinal, and neurologic toxicity that can complicate adherence. Recent phase 3 studies (HELEN-006 and NeoCARHP) have shown that omitting carboplatin can achieve noninferior pCR rates with improved tolerability; in this trial, the anbenitamab-HB1801 benefit held up regardless of carboplatin use, suggesting the regimen could work across a broad spectrum of ERBB2-positive patients. The authors also draw a comparison to the DESTINY-Breast11 trial, in which a sequential regimen of trastuzumab deruxtecan (T-DXd) followed by THP achieved a pCR rate of 67.3% in a high-risk population — noting that a 6-cycle anbenitamab-HB1801 regimen achieved a comparable efficacy profile (66.7% tpCR among carboplatin recipients) while potentially avoiding T-DXd's pulmonary toxicity risks.
Limitations
Because anbenitamab and HB1801 were tested only in combination, the trial's design cannot isolate which agent is driving the tpCR benefit, or whether a different pairing (or either agent alone) would perform as well. Median follow-up at this data cutoff was less than 8 months, so longer-term outcomes such as event-free survival and overall survival have not yet been reported, and durability of the pCR advantage is unknown. All 61 participating sites were in China, and whether these results generalize to other populations or health systems is not addressed by this trial. The ECOG performance status 1 subgroup showed a result favoring the control arm, which the authors attribute to small sample size rather than a genuine reversal, but the trial was not powered to resolve that question.
In this phase 3 registrational trial, neoadjuvant anbenitamab plus HB1801 raised total pathological complete response to 62.4% versus 51.2% with standard trastuzumab, pertuzumab, and docetaxel in stage II–III ERBB2-positive breast cancer, with a similar grade 3/4 adverse event rate between arms. Because the two drugs were tested only as a combination and follow-up is under 8 months, the trial cannot show which agent drives the benefit, and longer-term outcomes such as event-free survival are not yet available.