Inetetamab-Pyrotinib Regimen Shows High pCR in HER2-Positive Breast Cancer

According to results from the phase 2 neoPICD trial (NCT06234137), presented during a press briefing ahead of the 2026 ASCO Breakthrough Meeting, neoadjuvant inetetamab plus pyrotinib and chemotherapy produced a total pathologic complete response (tpCR) rate of 60.2% in patients with HER2-positive locally advanced breast cancer and high tumor burden.

The prospective, multicenter, single-arm trial enrolled 124 patients with stage II to III, nonmetastatic HER2-positive breast cancer across 7 centers in China; 108 patients were evaluable for efficacy. Patients received neoadjuvant inetetamab (8 mg/kg loading dose, then 6 mg/kg intravenously every 3 weeks for 6 cycles), pyrotinib (400 mg orally once daily for 18 weeks), and docetaxel (75 mg/m²) plus carboplatin (area under the curve of 6) every 3 weeks for 6 cycles, followed by surgery 2 to 4 weeks after completion of neoadjuvant therapy. Patients then continued inetetamab and pyrotinib to complete 1 year of anti-HER2 therapy.

Study Design

The primary end point was tpCR (ypT0/is, ypN0); secondary end points included breast pathologic complete response (bpCR; ypT0/is), objective response rate (ORR), safety, immunogenicity, and survival outcomes. Sample size was calculated using a Simon 2-stage design, with a null tpCR rate of 45% and an alternative rate of 60% (1-sided α = .05; power = 90%). Patients were enrolled between December 2021 and October 2025.

Efficacy Results

Among the 108 efficacy-evaluable patients, tpCR occurred in 65 patients (60.2%; 95% CI, 50.8%-69.6%), and bpCR occurred in 65.7% (95% CI, 56.6%-74.8%) of patients. The ORR was 92.6% (95% CI, 87.6%-97.6%), and the disease control rate was 100%.

Responses were more pronounced among patients with hormone receptor (HR)-negative disease than among those with HR-positive disease, with tpCR rates of 73.3% vs 43.8% and bpCR rates of 76.7% vs 52.1%, respectively. On multivariate analysis, HR status was an independent predictor of efficacy (P <.05); favorable responses were also associated with premenopausal status, smaller tumor size, earlier nodal stage, lower disease stage, higher Ki-67 index, and higher histologic grade.

Safety

The most common adverse events were diarrhea, anemia, nausea and vomiting, and decreased appetite. No treatment-related deaths were reported.

“This regimen demonstrates favorable efficacy and a manageable safety profile, offering a better option for patients with locally advanced disease with high tumor burden, thereby addressing a critical unmet need in the current treatment landscape,” said Chenghui Yang, PhD, Department of Breast Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China, told a press briefing ahead of the 2026 ASCO Breakthrough Meeting.

Clinical Context and Limitations

Inetetamab is a HER2-targeted monoclonal antibody engineered for enhanced antibody-dependent cellular cytotoxicity, and pyrotinib is an oral, irreversible pan-HER tyrosine kinase inhibitor targeting HER1, HER2, and HER4; both agents were developed in China and are not approved by the FDA. Neoadjuvant docetaxel plus carboplatin with trastuzumab and pertuzumab remains the standard regimen for HER2-positive breast cancer, but 22% to 25% of patients develop resistance to monoclonal antibody-based anti-HER2 therapy, a gap the investigators said this combination may help address.

Longer follow-up is planned to evaluate survival outcomes, including overall survival, and the investigators noted that a larger, randomized phase 3 trial comparing inetetamab plus pyrotinib with trastuzumab- and pertuzumab-based treatment may be warranted.

REFERENCES

1. Yang C, Xu Y, Wang O. Inetetamab combined with pyrotinib for neoadjuvant treatment of HER2-positive locally advanced breast cancer (neoPICD): A prospective, multicenter, single-arm phase II trial. J Clin Oncol. 2026;44(suppl 19):abstr 27. doi:10.1200/JCO.2026.44.19_suppl.27

2. Barbor M. HER2-targeted regimen yields high pathologic complete response rate in locally advanced breast cancer. The ASCO Post. August 6, 2026. Accessed August 7, 2026. https://tinyurl.com/28pxwmrx