This study will evaluate whether adding QL1706 (iparomlimab and tuvonralimab) to neoadjuvant endocrine therapy improves tumor response in patients with hormone receptor-positive (HR-positive), human epidermal growth factor receptor 2-negative (HER2-negative) breast cancer who have had a poor response to neoadjuvant chemotherapy.
Approximately 40 participants whose tumors have decreased by less than 40% on magnetic resonance imaging after two cycles of neoadjuvant TAC chemotherapy will be randomly assigned in a 1:1 ratio to receive either an aromatase inhibitor plus a CDK4/6 inhibitor or the same treatment combined with QL1706. Premenopausal and perimenopausal participants will also receive ovarian function suppression.
The main outcome is the objective response rate during the study treatment period. Pathological response, changes in Ki-67, treatment safety, and changes in the tumor immune microenvironment will also be evaluated.
Female participants aged 18 to 75 years.
Histologically or pathologically confirmed HR-positive/HER2-negative early or locally advanced breast cancer, classified as stage IIB-IIIC, with a poor response to two cycles of neoadjuvant TAC chemotherapy. Chemotherapy sensitivity is defined as a reduction in tumor size of at least 40% on magnetic resonance imaging (MRI), whereas a poor response is defined as a reduction in tumor size of less than 40%.
At least one measurable lesion according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1).
No prior antitumor treatment other than the two cycles of neoadjuvant TAC chemotherapy specified in this study, including no prior immune checkpoint inhibitor therapy.
Known hypersensitivity to any study drug or any of its excipients.
Inflammatory breast cancer, bilateral breast cancer, or advanced breast cancer with distant metastases.
A history of another malignancy within the past 5 years, except for malignancies treated with curative intent.
Serious concomitant diseases, including extensive interstitial pneumonitis requiring pharmacological treatment; active or uncontrolled infection, including tuberculosis or human immunodeficiency virus infection; decompensated liver disease; active hepatitis; active bleeding; a history of cerebrovascular events or pulmonary embolism; active, known, or suspected autoimmune disease; or an active infection currently requiring systemic anti-infective therapy.
Parallel
Iparomlimab and Tuvonralimab (QL1706)
DrugIparomlimab and tuvonralimab (QL1706) will be administered intravenously at 5 mg/kg on Day 1 of each 3-week cycle for six cycles.
Aromatase Inhibitor (AI)
DrugParticipants will receive exemestane, anastrozole, or letrozole. The specific aromatase inhibitor, dose, and administration schedule will be selected according to the applicable prescribing information or clinical guidelines and will be continued throughout the approximately 18-week neoadjuvant treatment period.
CDK4/6 inhibitor
DrugParticipants will receive abemaciclib or ribociclib. The specific CDK4/6 inhibitor, dose, and administration schedule will be selected according to the applicable prescribing information or clinical guidelines and will be continued throughout the approximately 18-week neoadjuvant treatment period.
Ovarian function suppression
DrugPremenopausal and perimenopausal participants will receive ovarian function suppression with goserelin, leuprorelin, or triptorelin. The specific agent, dose, and administration schedule will follow the applicable prescribing information or clinical guidelines.
Objective Response Rate (ORR)
The proportion of participants whose best overall response is complete response (CR) or partial response (PR), as assessed by computed tomography or magnetic resonance imaging according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). ORR will be calculated as the number of participants achieving CR or PR divided by the total number of participants included in the efficacy analysis, multiplied by 100%.
Breast Pathological Complete Response Rate (bpCR)
Total Pathological Complete Response Rate (tpCR)
Miller-Payne Grade
Pathological response of the primary breast tumor will be assessed using the Miller-Payne grading system, which ranges from Grade 1 to Grade 5. Grade 1 indicates no or minimal reduction in tumor cells, whereas Grade 5 indicates no identifiable malignant cells at the primary tumor site. A higher grade indicates a better pathological response to treatment.
Residual Cancer Burden (RCB) Class
Residual cancer burden will be assessed in the resected breast and regional lymph nodes and classified as RCB-0, RCB-I, RCB-II, or RCB-III. RCB-0 indicates no residual invasive cancer, whereas RCB-III indicates extensive residual disease. A higher RCB class indicates a greater residual tumor burden and a worse pathological response to treatment.
Change in Tumor Immune-Cell Infiltration
Change in PD-1 Expression
Change in PD-L1 Expression
Change in CTLA-4 Expression
Click on the lead sponsor to view all of their trials.
This trial is not recruiting at the moment. You can still explore other options:
