A Phase III Study of KN026 in Combination With HB1801 ± Carboplatin as Neoadjuvant Treatment for Early or Locally Advanced HER2-Positive Breast Cancer

A Randomized, Controlled, Open-label, Multicenter, Phase III Clinical Trial to Compare the Efficacy and Safety of KN026 Combined With HB1801 ± Carboplatin Versus Trastuzumab Combined With Pertuzumab and Docetaxel ± Carboplatin in Neoadjuvant Treatment of Early or Locally Advanced HER2-positive Breast Cancer.

This randomized, controlled, open-label, multicenter study will evaluate the safety and efficacy of KN026 in combination with HB1801 ± Carboplatin as neoadjuvant therapy in patients with early or locally advanced HER2-positive breast cancer.

In this randomized, controlled, open-label, multicenter Phase III trial, treatment-naive patients with HER2-positive breast cancer were centrally randomized (1:1) and stratified by disease stage, hormone receptor status, and the planned use of Carboplatin. Participants received six cycles of: neoadjuvant therapy: KN026 combined with HB1801 ± Carboplatin (Experimental) or Trastuzumab plus Pertuzumab and Docetaxel ± Carboplatin (Active Comparator). The primary endpoint was pathological complete response (pCR) in the breast, evaluated in the intention-to-treat (ITT) population.

Inclusion Criteria:

1. Voluntarily participate in the experiment and sign the informed consent;
2. Aged >= 18 years;
3. Histologically and cytologically confirmed primary invasive carcinoma of the breast with early (T2-3, N0-1, M0) or locally advanced stage (T2-3, N2-3, M0; T4, any N, M0) (AJCC 8th Edition);
4. ECOG PS 0-1;
5. HER2 positive (HER2+++ by IHC or HER2++ by IHC and ISH+);
6. Agree to receive surgical treatment for breast cancer in the participating research unit when the surgical standard is reached after neoadjuvant therapy;
7. Adequate organ and bone marrow function (no blood transfusions or hematopoietic stimulating factor classes within 14 days prior to the test);
8. Women of childbearing potential and male participants with partners of childbearing potential must agree to use effective contraception (as defined by the protocol) by the participant and/or partner for the duration of the study treatment and for at least 3 months (Docetaxel and HB1801) or 7 months (Pertuzumab, trastuzumab, KN026, and Carboplatin) after the last dose of study drug;

Exclusion Criteria:

1. Inflammatory or bilateral breast cancer;
2. History of non-breast malignancies within the 3 years prior to study entry, except for carcinoma in situ of the cervix or breast, and basal cell and squamous cell carcinomas of the skin, etc.;
3. The researchers determine that there are contraindications for breast cancer surgery;
4. Participants who underwent primary lumpectomy and/or axillary lymph node dissection biopsy prior to randomization (except for diagnostic biopsy of primary breast cancer or surgery for benign breast tumors);
5. Any previous systemic chemotherapy, endocrine therapy or anti HER2 biological therapy or local radiotherapy for breast cancer;
6. Sensitivity to any of the study medications or any of the ingredients or excipients of these medications;
7. Participants with known allergies and/or contraindications to glucocorticoids;
8. Have a congenital or acquired immune deficiency (such as HIV infection); 9 . Serious cardiac or cardiovascular disease or condition; 10 Serious chronic or active infections requiring intravenous antimicrobial, antifungal, or antiviral therapy were present within 14 days prior to randomization.

11. Patients who had undergone major organ surgery (excluding biopsy) within 28 days before randomization and have not fully recovered.

12. Potent inhibitors or inducers of CYP3A4 were used within 14 days before randomization or continued use was required.

13. Being enrolled in other clinical trials (except for non-interventional clinical trials or a follow-up period in an interventional trial) or at randomization was less than 4 weeks from the end of the previous clinical trial (end of treatment).

14. Pregnant or lactating. 15. The existence of other conditions that may interfere with the participant's study procedures or that do not correspond to the participant's maximum benefit from participating in the study or to the findings of the imaging study, such as a history of neurological or mental illness, alcohol abuse, drug use or substance abuse, any other disease or condition of clinical significance.