QL1706 Plus Neoadjuvant Endocrine Therapy in HR-Positive/HER2-Negative Breast Cancer With a Poor Response to Neoadjuvant Chemotherapy

Patients with HR‐positive/HER2‐negative breast cancer may have an inadequate response toneoadjuvant chemotherapy, and an optimal subsequent neoadjuvant treatment strategy forthis population has not been established. QL1706 is a bifunctional combination antibodyconsisting of iparomlimab, which targets programmed cell death protein 1 (PD‐1), andtuvonralimab, which targets cytotoxic T‐lymphocyte‐associated protein 4 (CTLA‐4).Simultaneous inhibition of these immune checkpoints may enhance antitumor immuneactivity. This study will explore whether the addition of QL1706 to endocrine therapy andCDK4/6 inhibition improves tumor response in patients who have had a poor early responseto neoadjuvant chemotherapy.This is an exploratory, open‐label, prospective, randomized controlled study.Approximately 40 women with stage IIB‐IIIC HR‐positive/HER2‐negative early or locallyadvanced breast cancer will be enrolled. Eligible participants must have received twocycles of neoadjuvant TAC chemotherapy and have a reduction in tumor size of less than40% on magnetic resonance imaging. Participants will be randomly assigned in a 1:1 ratioto the experimental arm or the active comparator arm.Participants in the active comparator arm will receive an aromatase inhibitor plus aCDK4/6 inhibitor. Participants in the experimental arm will receive the same treatmentcombined with QL1706 at 5 mg/kg by intravenous infusion on Day 1 of each 3‐week cycle forsix cycles. Premenopausal and perimenopausal participants will receive ovarian functionsuppression. Surgery will be performed after completion of neoadjuvant treatment based onclinical assessment.The primary outcome is the objective response rate according to Response EvaluationCriteria in Solid Tumors version 1.1. Secondary outcomes include breast pathologicalcomplete response, total pathological complete response, Miller‐Payne grade, residualcancer burden class, changes in Ki‐67 expression, and the incidence of immune‐related andother adverse events. Exploratory analyses will assess changes in the tumor immunemicroenvironment, including immune‐cell infiltration and the expression of PD‐1,programmed death‐ligand 1, and CTLA‐4, using blood and tumor specimens collected atprotocol‐specified time points.