A Study of BL-M07D1 With or Without Pertuzumab Versus Docetaxel + Carboplatin + Trastuzumab + Pertuzumab in Neoadjuvant Therapy for HER2-Positive Breast Cancer

A Randomized Controlled Phase II/III Clinical Study of BL-M07D1 With or Without Pertuzumab Versus Docetaxel + Carboplatin + Trastuzumab + Pertuzumab in Neoadjuvant Therapy for HER2-Positive Breast Cancer

This trial is a registered phase III, randomized, open and multicenter study to evaluate the efficacy and safety of BL-M07D1 with or without Pertuzumab in the neoadjuvant treatment of HER2-positive breast cancer. The study is divided into a single-arm study phase (Phase II) and a randomized controlled study phase (Phase III).

Inclusion Criteria:

1. Voluntarily signed informed consent and followed the program requirements;
2. Females ≥18 and ≤75 years of age at the time of signing the informed consent;
3. Expected survival time ≥6 months;
4. Patients with HER2-positive invasive breast cancer confirmed by histologic examination;
5. Clear hormone receptor (HR) status;
6. Clear clinical stage II-III based on American Joint Committee on Cancer (AJCC) staging 8th edition prior to neoadjuvant therapy;
7. Primary subjects without antitumor therapy for breast cancer;
8. Subjects consenting to mastectomy or breast-conserving surgery at the end of neoadjuvant therapy;
9. Radical surgery to the last dose of neoadjuvant therapy at least 2 weeks apart and up to 6 weeks apart;
10. Physical status score ECOG 0 or 1;
11. Organ function levels must be met provided that blood transfusions are not permitted within 14 days prior to the first administration of study drug, colony-stimulating factors are not permitted, and so on;
12. For premenopausal women of childbearing potential a pregnancy test must be performed within 7 days prior to initiation of treatment, serum pregnancy must be negative, and must be non-lactating; all enrolled patients should be using adequate and highly effective contraception throughout the treatment cycle and for 7 months after completion of treatment.

Exclusion Criteria:

1. Diagnosis of stage IV metastatic breast cancer;
2. Bilateral breast cancer;
3. Prior history of any breast cancer (unilateral or contralateral) other than lobular carcinoma in situ (LCIS);
4. Diagnosis of another primary malignancy within 5 years prior to first dose;
5. History of severe cardiovascular or cerebrovascular disease within 6 months prior to screening;
6. Prolonged QT interval, complete left bundle branch block, degree III atrioventricular block, and frequent and uncontrollable arrhythmias;
7. Poorly controlled hypertension (systolic blood pressure > 150 mmHg or diastolic blood pressure > 100 mmHg);
8. Complicated lung disease resulting in severely impaired lung function;
9. History of ILD / interstitial pneumonitis requiring steroid hormone therapy, current ILD / interstitial pneumonitis, or suspected of having such a disease, etc;
10. Human immunodeficiency virus antibody positivity, active hepatitis B virus infection, cirrhosis, or hepatitis C virus infection;
11. Severe infection within 4 weeks prior to first dose of study drug; active pulmonary inflammation present at screening;
12. Ongoing treatment with >10 mg/d prednisone systemic corticosteroid therapy or equivalent anti-inflammatory active drug or any form of immunosuppressive therapy within 2 weeks prior to the first dose;
13. Known hypersensitivity to the study therapeutic drug or any study drug excipients or other monoclonal antibodies;
14. Patients who are not suitable to receive the investigational drug (paclitaxel, patulizumab, trastuzumab);
15. Have a history of autologous or allogeneic stem cell transplantation or organ transplantation;
16. Suffering from severe neurological or psychiatric disorders;
17. Subjects with clinically significant bleeding or significant bleeding tendency within 4 weeks prior to signing the information;
18. Intestinal obstruction, Crohn's disease, ulcerative colitis or chronic diarrhea;
19. Subjects who are scheduled to receive a live vaccine or who have received a live vaccine within 28 days prior to the first dose;
20. Presence of other serious physical, laboratory test abnormalities or poor compliance that may increase the risk of participation in the study or interfere with the study results, as well as patients who, in the opinion of the investigator, are not suitable for participation in this study.