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 .
Dai et al. (Wed,) studied this question.