Delayed serplulimab combined with nab-paclitaxel and epirubicin in high-risk, early HR+/HER2− breast cancer (HELEN-B 018): A multicenter, single-arm, phase 2 trial.

609 Background: Novel treatment options are needed to improve long-term outcome of high-risk early HR+/HER2− breast cancer. Evidence shows a programmed death 1 inhibitor combined with chemotherapy increases pCR rates in this subtype. We aimed to evaluate the efficacy and safety of serplulimab combined with nab-paclitaxel and epirubicin in high-risk, early HR+/HER2− breast cancer. Methods: This multicentre, single-arm, phase 2 trial was conducted in China at 6 hospitals. Patients were eligible if they were 18 years or older, with previously untreated early HR+/HER2- breast cancer, and Ki-67 greater than or equal to 20%, and had an Eastern Cooperative Oncology Group (ECOG) performance status of 0–1. Participants were allocated to intravenous nab-paclitaxel (260 mg/m 2 ) and intravenous epirubicin (75 mg/m 2 ) on the first day and intravenous serplulimab (4.5mg/kg) on the third day of the treatment cycle. 6 cycles of neoadjuvant treatment were administered. The primary outcome was pCR (defined as ypN0 or ypT0/is), assessed in the full analysis set, which included all patients who had started the trial treatment. We estimated that with enrollment of 109 participants, this trial would have 80% power to detect a true difference in the percentage of patients with a pCR of 10% at a one-sided alpha level of 0.025, with a dropout rate of 10%. This study is registered with ClinicalTrials.gov (NCT06394661). Results: Between Apr 28, 2024, and May 24, 2025, 136 patients were assessed for eligibility; 27 were ineligible and 109 participants were enrolled in this study, of whom 101 participants started trial treatment. Median age of the participants was 49 [range, 30 to 72] years at the time of enrolment, and 45 (44.6%) were PD-L1 positive (CPS ≥1). pCR was achieved in 23 patients (22.8%, 95%CI 15.3%-32.4%). PCR rate was numerically higher in patients with PD-L1 positive tumors (44.4%, 95%CI 30.0%-59.9%). During the neoadjuvant phase, 30 (29.7%) patients experienced grade 3 or higher treatment-related adverse events. The most common grade 3–4 adverse events were increased alanine aminotransferase (ALT; six [5.9%]), increased aspartate aminotransferase (AST; five [5.0%]), and diarrhea (four [4.0%]), There were no treatment-related deaths. Conclusions: Delayed serplulimab combined with nab-paclitaxel and epirubicin showed promising anti-tumour activity and manageable safety in patients with HR+/HER2− breast cancer; the pCR rate was higher in PD-L1 expression tumor. These findings support further evaluation of this regimen in randomized controlled trials. Clinical trial information: NCT06394661 .