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

NCT07782840 | Not Yet Recruiting Phase 2

• 2 other identifiers: 2026KY043LH20250010
• Study Type: interventional
• Target: 40
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (1)

• 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%.

  From randomization through the preoperative assessment after six treatment cycles, approximately 18 weeks

Secondary Outcomes (6)

• Breast Pathological Complete Response Rate (bpCR)

  At surgery after completion of six treatment cycles, approximately 18 weeks after randomization

• Total Pathological Complete Response Rate (tpCR)

  At surgery after completion of six treatment cycles, approximately 18 weeks after randomization

• Miller-Payne Grade

  At surgery after completion of six treatment cycles, approximately 18 weeks after randomization

• Residual Cancer Burden (RCB) Class

  At surgery after completion of six treatment cycles, approximately 18 weeks after randomization

• Incidence of Immune-Related Adverse Events

  From the first dose of study treatment through 30 days after the last dose, approximately 22 weeks

Other Outcomes (5)

• Change in Tumor Immune-Cell Infiltration

  From baseline to surgery after completion of six treatment cycles, approximately 18 weeks

• Change in PD-1 Expression

  From baseline to surgery after completion of six treatment cycles, approximately 18 weeks

• Change in PD-L1 Expression

  From baseline to surgery after completion of six treatment cycles, approximately 18 weeks

Study Arms (2)

QL1706 Plus Endocrine Therapy

EXPERIMENTAL

Participants will receive an aromatase inhibitor plus a CDK4/6 inhibitor and QL1706. QL1706 will be administered intravenously at 5 mg/kg on Day 1 of each 3-week cycle for six cycles. The aromatase inhibitor and CDK4/6 inhibitor will be administered according to their respective prescribing information or applicable clinical guidelines throughout the neoadjuvant treatment period. Premenopausal and perimenopausal participants will also receive ovarian function suppression.

Drug: Iparomlimab and Tuvonralimab (QL1706); Drug: Aromatase Inhibitor (AI); Drug: CDK4/6 inhibitor; Drug: Ovarian function suppression

Endocrine Therapy

ACTIVE COMPARATOR

Participants will receive an aromatase inhibitor plus a CDK4/6 inhibitor according to the respective prescribing information or applicable clinical guidelines throughout the neoadjuvant treatment period. Premenopausal and perimenopausal participants will also receive ovarian function suppression.

Drug: Aromatase Inhibitor (AI); Drug: CDK4/6 inhibitor; Drug: Ovarian function suppression

Interventions

Iparomlimab and Tuvonralimab (QL1706) DRUG

Iparomlimab and tuvonralimab (QL1706) will be administered intravenously at 5 mg/kg on Day 1 of each 3-week cycle for six cycles.

QL1706 Plus Endocrine Therapy

Aromatase Inhibitor (AI) DRUG

Participants 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.

Also known as: Exemestane, Anastrozole, Letrozole

Endocrine Therapy; QL1706 Plus Endocrine Therapy

CDK4/6 inhibitor DRUG

Participants 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.

Also known as: Abemaciclib, Ribociclib

Endocrine Therapy; QL1706 Plus Endocrine Therapy

Ovarian function suppression DRUG

Premenopausal 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.

Also known as: Goserelin, Leuprorelin, Triptorelin

Endocrine Therapy; QL1706 Plus Endocrine Therapy

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Life expectancy of at least 12 weeks.
• No coagulation abnormalities.
• Normal cardiac function, a normal electrocardiogram, and a left ventricular ejection fraction of at least 55%.
• Willingness to provide tumor tissue and/or blood samples at baseline and after treatment for biomarker analyses. Participants with insufficient tumor tissue or those unwilling to provide biological samples may be enrolled only with the investigator's approval.
• Adequate major organ function, as defined by the following laboratory criteria: absolute neutrophil count greater than 1.5 × 10\^9/L; platelet count greater than 100 × 10\^9/L; hemoglobin greater than 100 g/L; total serum bilirubin less than 1.5 × the upper limit of normal (ULN); alanine aminotransferase and aspartate aminotransferase less than 3 × ULN; and serum creatinine no greater than 1.5 × ULN.
• Ability to understand and comply with the study requirements and willingness to provide written informed consent.

You may not qualify if:

• 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.
• Active brain metastases or leptomeningeal metastases, unless the metastases have been treated and are stable.
• Pregnancy, planned pregnancy, or breastfeeding.
• Any other condition that, in the investigator's opinion, makes the participant unsuitable for enrollment.

Sponsors & Collaborators

• Hebei Medical University Fourth Hospital: lead

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Aromatase Inhibitors; exemestane; Anastrozole; Letrozole; abemaciclib; ribociclib; Goserelin; Leuprolide; Triptorelin Pamoate

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Steroid Synthesis Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Estrogen Antagonists; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Gonadotropin-Releasing Hormone; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins

Central Study Contacts

Li Ma, MD

CONTACT

+86 86296348; 47500562@hebmu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor and Chief Physician

Model Details: Eligible participants will be randomly assigned in a 1:1 ratio to two parallel treatment arms. The experimental arm will receive an aromatase inhibitor plus a CDK4/6 inhibitor and QL1706, whereas the active comparator arm will receive an aromatase inhibitor plus a CDK4/6 inhibitor.

Study Record Dates

• First Submitted: August 20, 2026
• First Posted: August 24, 2026
• Study Start (Estimated): October 1, 2026
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): December 1, 2028
• Last Updated: August 26, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will not share