A Study Comparing BL-M07D1 With T-DM1 in Patients With Unresectable Locally Advanced or Metastatic HER2-positive Breast Cancer

A Randomized Controlled Phase III Clinical Study Comparing BL-M07D1 With T-DM1 in Patients With Unresectable Locally Advanced or Metastatic HER2-positive Breast Cancer

This study is a registered phase III, randomized, open-label, multicenter study to evaluate the efficacy and safety of BL-M07D1 in patients with unresectable locally advanced or metastatic HER2-positive breast cancer who had failed previous treatment with taxanes and trastuzumab.

Inclusion Criteria:

1. Voluntarily sign the informed consent and follow the requirements of the protocol;
2. No gender limit;
3. Age ≥18 years old and ≤75 years old at the time of signing the informed consent;
4. expected survival time ≥3 months;
5. Patients with histologically or cytologically confirmed, unresectable, locally advanced or metastatic HER2-positive breast cancer;
6. Provide the latest tumor tissues to the central laboratory for HER2 and HR detection;
7. Must have at least one measurable target lesion that meets the RECIST v1.1 definition;
8. ECOG 0 or 1;
9. Toxicity of previous antineoplastic therapy has returned to ≤ grade 1 defined by NCI-CTCAE v5.0;
10. No severe cardiac dysfunction, left ventricular ejection fraction ≥50%;
11. Blood transfusion is not allowed within 14 days before the first use of the study drug, and no cell growth factor is allowed;
12. Coagulation function: international normalized ratio (INR) ≤1.5 and activated partial thromboplastin time (APTT)≤1.5×ULN;
13. Urine protein ≤2+ or < 1000mg/24h;
14. For premenopausal women with childbearing potential, a pregnancy test must be performed within 7 days before the initiation of treatment, serum pregnancy must be negative, and must be non-lactating; All enrolled patients (male or female) were advised to use adequate barrier contraception throughout the treatment cycle and for 7 months after the end of treatment.

Exclusion Criteria:

1. Received chemotherapy with mitomycin C and nitrosourea within 6 weeks before the first dose, received surgery, chemotherapy, immunotherapy, etc. Within 4 weeks before the first dose, received endocrine therapy, palliative radiotherapy, and anti-tumor therapy approved by NMPA within 2 weeks before the first dose;
2. Previous use of HER2-ADC in the metastatic background;
3. Prior treatment with an ADC drug containing a camptothecin derivative (topoisomerase I inhibitor) as a toxin;
4. The history of severe cardiovascular and cerebrovascular diseases in the past six months was screened;
5. Complicated with pulmonary diseases leading to severe impairment of lung function;
6. History of ILD/interstitial pneumonia, current ILD/interstitial pneumonia, or suspected ILD/interstitial pneumonia; According to CTCAE v5.0 was defined as ≥ grade 3 pulmonary disease and ≥ grade 2 radiation pneumonitis;
7. QT prolongation, complete left bundle branch block, III degree atrioventricular block, frequent and uncontrollable arrhythmia;
8. Other primary malignancies diagnosed within 5 years before the first dose;
9. Poorly controlled hypertension (systolic blood pressure &gt; 150 mmHg or diastolic blood pressure &gt; 100 mmHg);
10. Patients with active central nervous system metastases;
11. Patients with a history of allergy to recombinant humanized antibody or to any of the excipents of BL-M07D1;
12. Patients with known hypersensitivity or delayed hypersensitivity to certain components of T-DM1 or similar drugs, or known contraindications to T-DM1;
13. History of autologous or allogeneic stem cell transplantation or organ transplantation;
14. Anthracycline-equivalent cumulative dose of adriamycin > 360 mg/m2;
15. Human immunodeficiency virus antibody positive, active hepatitis B virus infection, cirrhosis, or hepatitis C virus infection;
16. Serious infection within 4 weeks before the first dose of study drug; There was active pulmonary inflammation at the time of screening;
17. Patients with massive or symptomatic effusions or poorly controlled effusions;
18. Receiving active antiinflammatory drugs or any form of immunosuppressive therapy before randomization;
19. A history of severe neurological or psychiatric illness;
20. Subjects with clinically significant bleeding or obvious bleeding tendency within 4 weeks before signing the informed consent;
21. Intestinal obstruction, Crohn's disease, ulcerative colitis or chronic diarrhea;
22. Subjects who are scheduled to receive live vaccine or receive live vaccine within 28 days before the first dose;
23. Patients who were deemed by the investigator to be ineligible for the study.