Neoadjuvant QL1706 plus chemotherapy for early HR-positive/HER2-negative breast cancer

QL1706 Combined With PE Compared With PE for the Neoadjuvant Treatment of HR+/HER2- Breast Cancer

This trial tests whether adding QL1706 to pre-surgery chemotherapy improves the chance of a complete tumor response in people with early HR+/HER2- breast cancer.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 238 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Henan Cancer Hospital (Government)
• Drugs / interventions: chemotherapy
• Locations: 1 site (Zhengzhou)
• Trial ID: NCT06967103 on ClinicalTrials.gov

What this trial studies

Adults with early-stage hormone receptor–positive, HER2-negative breast cancer and high proliferation (Ki67 ≥20%) will receive either QL1706 combined with nab‑paclitaxel or nab‑paclitaxel alone every three weeks for six cycles before surgery. All participants will undergo definitive breast surgery to determine pathological complete response (pCR), the primary endpoint, and those in the QL1706 arm will receive adjuvant QL1706 every three weeks for up to six months from treatment start. Safety and adverse events will be monitored throughout treatment and follow-up. Enrollment is limited to patients who have not received prior systemic therapy and who can provide tumor tissue for analysis.

Who should consider this trial

Good fit: Ideal candidates are adults with operable HR+/HER2- breast cancer (cT2–T4d or cT1c with node-positive disease), Ki67 ≥20%, no prior systemic therapy, and who can undergo planned radical surgery.

Not a fit: Patients with HER2-positive disease, low-proliferation tumors (Ki67 <20%), metastatic disease, prior systemic therapy for breast cancer, or who cannot tolerate chemotherapy or immunotherapy are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, adding QL1706 could raise pCR rates before surgery and potentially improve long-term outcomes for patients with early HR+/HER2- breast cancer.

How similar studies have performed: Checkpoint inhibitors have shown benefit mainly in triple-negative breast cancer, while PD-1 plus CTLA-4 combinations in HR+/HER2- disease remain largely experimental with limited positive data to date.

Eligibility criteria

Inclusion Criteria

Subjects meeting all of the following criteria are eligible for inclusion in this study:

Voluntarily participates in the study, signs the informed consent form, and demonstrates good compliance.

Female, aged ≥18 years .

Evaluated by the research center as eligible to tolerate and scheduled to undergo radical breast cancer surgery, with no prior systemic anti-tumor therapy for breast cancer.

cT2 - T4d N0-N3, or cT1c with axillary lymph node metastasis confirmed clinically and pathologically；

Histologically and/or cytologically confirmed hormone receptor-positive (HR+) breast cancer (estrogen receptor \[ER\] or progesterone receptor \[PR\] nuclear staining \>1%) with Ki67 ≥20%.

HER2-negative breast cancer, defined as:

Negative in situ hybridization (ISH) results; or

Immunohistochemistry (IHC) status of 0, 1+, or 2+. If IHC is 2+, ISH (e.g., FISH, CISH, SISH) must be negative.

Willing to provide fresh or archived tumor tissue samples.

At least one measurable lesion per RECIST 1.1 criteria.

Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.

Adequate organ function, defined as:

Hematology:

Hemoglobin ≥90 g/L

Absolute neutrophil count ≥1.5 × 10⁹/L

Platelet count ≥100 × 10⁹/L.

Biochemistry:

ALT and AST ≤2.5 × ULN (≤5 × ULN if liver metastases present);

Total bilirubin ≤1.5 × ULN;

Serum creatinine ≤1.5 × ULN or creatinine clearance (CCr) ≥60 mL/min.

Coagulation:

Activated partial thromboplastin time (APTT) ≤1.5 × ULN;

International normalized ratio (INR) ≤1.5 × ULN.

Cardiac function:

Left ventricular ejection fraction (LVEF) ≥50% by echocardiography.

Premenopausal or perimenopausal subjects must agree to use reliable and effective contraception or practice abstinence from the time of informed consent until at least 90 days after the last dose of study treatment.

Exclusion Criteria

Subjects meeting any of the following criteria will be excluded from this study:

Known severe hypersensitivity to macromolecular protein preparations, QL1706, albumin-bound paclitaxel, epirubicin hydrochloride, or their excipients.

Stage IV metastatic breast cancer or other conditions deemed ineligible for curative surgery after neoadjuvant therapy by the investigator.

Inflammatory breast cancer or bilateral primary breast cancer (including invasive or in situ carcinoma).

Major surgery or significant trauma within 28 days prior to the first dose.

Administration of live attenuated vaccines within 28 days before the first dose or anticipated during the study.

Systemic corticosteroids or immunosuppressive therapy within 14 days prior to the first dose or anticipated during the study.

Active autoimmune disease requiring systemic treatment within 2 years prior to enrollment, or history of autoimmune disorders.

Severe systemic infection within 28 days or active infection requiring intravenous/oral antibiotics within 14 days prior to the first dose.

Prior organ or allogeneic bone marrow transplantation or awaiting transplantation.

History or evidence of interstitial lung disease or active non-infectious pneumonitis.

Bleeding tendency or high risk of hemorrhage.

Thromboembolic events (e.g., cerebrovascular accident, pulmonary embolism) within 6 months prior to enrollment.

Congenital or acquired immunodeficiency (e.g., HIV infection).

Active hepatitis:

Hepatitis B: HBsAg-positive with HBV DNA ≥2000 IU/mL;

Hepatitis C: HCV antibody-positive with HCV RNA above the upper limit of normal.

Poorly controlled cardiac conditions, including:

NYHA Class II or higher heart failure or LVEF \<50%;

Unstable angina;

Myocardial infarction within 1 year;

QTc interval \>470 ms (female) on resting ECG.

Other malignancies within 5 years (excluding basal cell carcinoma or cervical carcinoma in situ).

Use of investigational drugs within 4 weeks prior to the first dose.

History or current diagnosis of neurological or psychiatric disorders (e.g., epilepsy, dementia).

History of pancreatitis.

Pregnancy, lactation, or refusal to use contraception.

Any other condition deemed inappropriate for participation by the investigator.

Where this trial is running

Zhengzhou

• Henan cancer hospital — Zhengzhou, China (Recruiting)

Study contacts

• Study coordinator: Zhenzhen Liu

Conditions Breast Cancer; HR+/HER2- Breast Cancer; PD1; CTLA4; breast cancer