A Prospective, Multicenter, Phase II Clinical Study of Postoperative Chemotherapy Combined With QL1706 for High-risk Triple-negative Breast Cancer.

A Prospective, Multicenter, Phase II Clinical Study of Postoperative Chemotherapy Combined With QL1706 for High-risk Triple-negative Breast Cancer.

This study is a prospective, multicenter, phase II clinical trial designed to evaluate the efficacy and safety of postoperative chemotherapy combined with QL1706 in patients with high-risk triple-negative breast cancer.

After enrollment, participants will receive 8 cycles of chemotherapy combined with QL1706. The standard chemotherapy regimen is the AC-T regimen (4 cycles of epirubicin plus cyclophosphamide, followed by 4 cycles of a taxane) - a Category I recommendation in the 2025 CSCO guidelines. The final choice of chemotherapy regimen is at the investigator's discretion. Starting from cycle 9, participants will receive QL1706 monotherapy as maintenance treatment. Dosing will continue until protocol-defined treatment discontinuation criteria are met, the participant experiences intolerable toxicity, or the participant withdraws informed consent. The maximum number of QL1706 dosing cycles is 17.

After completing treatment, participants will continue to undergo post-treatment safety follow-up and survival follow-up. For participants who discontinue treatment for reasons other than disease progression or death, tumor progression follow-up will also be conducted after treatment ends.

After enrollment, safety assessments will be performed every 3 weeks, and imaging evaluations will be performed every 12 weeks (±7 days) until confirmed disease progression per RECIST v1.1, initiation of another new anti-cancer therapy, withdrawal of informed consent, or death, whichever occurs first.

This study is a prospective, multicenter, phase II clinical trial designed to evaluate the efficacy and safety of postoperative chemotherapy combined with QL1706 in patients with high-risk triple-negative breast cancer.

After enrollment, participants will receive 8 cycles of chemotherapy combined with QL1706. The standard chemotherapy regimen is the AC-T regimen (4 cycles of epirubicin plus cyclophosphamide, followed by 4 cycles of a taxane) - a Category I recommendation in the 2025 CSCO guidelines. The final choice of chemotherapy regimen is at the investigator's discretion. Starting from cycle 9, participants will receive QL1706 monotherapy as maintenance treatment. Dosing will continue until protocol-defined treatment discontinuation criteria are met, the participant experiences intolerable toxicity, or the participant withdraws informed consent. The maximum number of QL1706 dosing cycles is 17.

After completing treatment, participants will continue to undergo post-treatment safety follow-up and survival follow-up. For participants who discontinue treatment for reasons other than disease progression or death, tumor progression follow-up will also be conducted after treatment ends.

After enrollment, safety assessments will be performed every 3 weeks, and imaging evaluations will be performed every 12 weeks (±7 days) until confirmed disease progression per RECIST v1.1, initiation of another new anti-cancer therapy, withdrawal of informed consent, or death, whichever occurs first.

Inclusion Criteria:

1. The participant voluntarily joins this study and signs the informed consent form.

2. Female breast cancer participants aged ≥18 and ≤75 years, with a histologically or cytologically confirmed diagnosis of TNBC (IHC 0, IHC 1+, or IHC 2+/ISH-) based on the most recent biopsy or other pathological specimen, according to the latest ASCO/CAP guidelines. Patients with low ER or PR expression (1%-10%) may also be included in this study.

3. Patients with high-risk TNBC (defined as lymph node-positive).

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

5. Agree to provide intraoperatively obtained tumor histopathological specimens (FFPE, at least 5 sections) for biomarker testing.

6. Expected survival ≥3 months.

7. Function of vital organs meets the following requirements (use of any blood components or cell growth factors within 14 days before the first dose is not allowed):

   • Absolute neutrophil count ≥1.5×10⁹/L;
   • Platelet count ≥100×10⁹/L;
   • Hemoglobin ≥90 g/L;
   • Serum albumin ≥30 g/L;
   • Thyroid-stimulating hormone (TSH) ≤1×ULN (if abnormal, FT3 and FT4 levels should also be assessed; if FT3 and FT4 are within normal range, the patient may be enrolled);
   • Serum total bilirubin ≤1.5×ULN;
   • ALT and AST ≤2.5×ULN; in the presence of liver metastases, ALT and AST ≤5×ULN;
   • ALP ≤2.5×ULN (in patients with liver or bone metastases, ALP ≤5×ULN);
   • Serum creatinine ≤1.5×ULN;
   • International normalized ratio (INR) ≤1.5×ULN (not receiving anticoagulation therapy).

8. Female participants who are not surgically sterilized or are of childbearing potential must use a medically approved contraceptive method (such as an intrauterine device, contraceptive pill, or condom) during the study treatment period and for 3 months after the end of the study treatment. Female participants of childbearing potential who are not surgically sterilized must have a negative serum or urine HCG test within 7 days before the first dose and must not be lactating.

Exclusion Criteria:

1. Presence of any active autoimmune disease or history of autoimmune disease (e.g., including but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hypophysitis, vasculitis, nephritis, hyperthyroidism); however, participants with the following conditions are allowed to enroll: vitiligo, psoriasis, alopecia not requiring systemic treatment; well-controlled type I diabetes mellitus; hypothyroidism stable on hormone replacement; childhood asthma that has completely resolved and requires no intervention in adulthood; asthma requiring bronchodilators for medical intervention is excluded.
2. Current use of immunosuppressants or systemic corticosteroid therapy for immunosuppressive purposes (dose >10 mg/day prednisone or equivalent) within 2 weeks prior to enrollment.
3. History of severe hypersensitivity reaction to other monoclonal antibodies.
4. Prior discontinuation of anti-PD-1/PD-L1 antibody therapy due to related toxicity.
5. Known history or evidence of interstitial lung disease or active non-infectious pneumonitis.
6. History of CNS metastases or current central nervous system (CNS) metastases. Baseline imaging to rule out brain metastases is not mandatory. Patients with unknown CNS metastasis status but with any clinical signs suggestive of CNS metastases are eligible only if CT and/or MRI scans rule out CNS metastases.
7. Previous history of other malignancies (except for patients with non-melanoma skin cancer or carcinoma in situ of the cervix, who are eligible; patients with other prior malignancies must have been disease-free for at least 3 years).
8. Hypertension poorly controlled with antihypertensive medication (systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg); achieving the above parameters with antihypertensive treatment is allowed. History of hypertensive crisis or hypertensive encephalopathy.
9. Within 6 months before first dose, known history of unstable angina, myocardial infarction (MI), or chronic heart failure (CHF), or known history of clinically significant arrhythmia requiring antiarrhythmic therapy (except stable atrial fibrillation), or left ventricular ejection fraction <50%.
10. Current thrombolytic or anticoagulant therapy; prophylactic use of low-dose aspirin or low-molecular-weight heparin is permitted.
11. Presence of pleural effusion, ascites, or pericardial effusion requiring drainage; patients may be enrolled if clinically stable after drainage as assessed by the investigator.
12. Arterial/venous thrombotic events occurring within 6 months before enrollment, such as cerebrovascular accident (including transient ischemic attack, cerebral hemorrhage, cerebral infarction), deep vein thrombosis, and pulmonary embolism.
13. Major vascular disease (e.g., aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis) within 6 months before start of study treatment.
14. Major surgery (excluding diagnostic procedures) within 4 weeks before start of study treatment, or anticipated need for major surgery during the study.
15. Urinalysis showing urine protein ≥++ and confirmed 24-hour urine protein >1.0 g.
16. Prior radiotherapy (except palliative radiotherapy for bone lesions), chemotherapy, or surgery (except biopsy) with completion (last dose) less than 4 weeks before the first study dose; last dose of antibody therapy less than 4 weeks before first study dose; molecular targeted therapy (including oral targeted drugs from other clinical trials) less than 5 half-lives before first study dose, or adverse reactions from prior treatment (excluding alopecia) not recovered to ≤CTCAE grade 1.
17. Active infection, unexplained fever ≥38.5°C within 7 days before dosing, or baseline white blood cell count >15×10⁹/L.
18. Congenital or acquired immunodeficiency (e.g., HIV infection); hepatitis B surface antigen (HBsAg) positive with HBV DNA ≥2000 IU/mL; or hepatitis C virus antibody positive.
19. Prior treatment with immune checkpoint inhibitors such as anti-PD-1, PD-L1, or anti-CTLA-4.
20. Receipt of live vaccine within 4 weeks before first study dose or possible vaccination during the study period.
21. As judged by the investigator, any other condition that may affect the study results or cause forced premature termination of the study, such as alcoholism, drug abuse, other serious diseases (including psychiatric illness) requiring concomitant treatment, severe laboratory abnormalities, or family/social factors that may affect patient safety.
22. Women who are pregnant or breastfeeding.