A Study Comparing BL-M07D1 With DS-8201 in Patients With HR-Positive, HER2-Low Expressing Recurrent/Metastatic Breast Cancer

A Randomized Controlled Phase II Clinical Study Comparing BL-M07D1 With DS-8201 in Patients With HR-Positive, HER2-Low Expressing Recurrent/Metastatic Breast Cancer

This trial is a randomized, open-label, multicenter Phase II study designed to evaluate the efficacy and safety of BL-M07D1 in patients with unresectable locally recurrent or metastatic HR-positive, HER2-low expressing breast cancer.

In this trial, the treatment group receives BL-M07D1, and the control group receives DS-8201.

Inclusion Criteria:

1. Voluntarily sign the informed consent form and agree to comply with the protocol requirements；
2. Female patients aged ≥18 years and ≤75 years at the time of signing the informed consent form；
3. Life expectancy ≥12 weeks；
4. Locally recurrent or metastatic breast cancer that is hormone receptor (HR)-positive and HER2-low expressing；
5. Provide adequate and recent tumor tissue specimens for central laboratory testing of HER2, HR, and other biomarkers as required；
6. Meet the prior treatment requirements as specified in the protocol；
7. Have at least one measurable target lesion per RECIST v1.1 criteria；
8. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1；
9. Toxicities from prior antitumor therapy have recovered to ≤Grade 1 per NCI-CTCAE v6.0；
10. Adequate organ function as defined in the protocol；
11. For premenopausal women of childbearing potential, a serum pregnancy test must be performed within 7 days prior to the start of treatment and must be negative; patients must not be breastfeeding. All enrolled patients (both male and female) must use adequate and highly effective contraceptive measures throughout the entire treatment period and for 7 months after the last dose of study treatment.

Exclusion Criteria:

1. Received surgery, curative radiotherapy, immunotherapy, or other systemic anti-tumor therapies within 4 weeks prior to the first dose;
2. Intolerance to the control drug or presence of other contraindications to the control drug;
3. Prior treatment with anti-HER2 therapy;
4. Prior treatment with an ADC (antibody-drug conjugate) using a camptothecin derivative as the payload;
5. History of severe cardiovascular or cerebrovascular disease within 6 months prior to screening;
6. Concurrent pulmonary disease resulting in severely impaired lung function;
7. History of ILD/interstitial lung disease requiring corticosteroid therapy, etc.;
8. QT interval prolongation, complete left bundle branch block, third-degree atrioventricular block, or frequent and uncontrolled arrhythmias;
9. Diagnosis of another primary malignancy within 5 years prior to the first dose;
10. Uncontrolled hypertension;
11. Active central nervous system (CNS) metastases;
12. History of severe allergic reactions to any excipient or component of the investigational drug;
13. History of autologous or allogeneic stem cell transplantation or organ transplantation;
14. Prior anthracycline treatment with a cumulative equivalent dose of doxorubicin > 360 mg/m²;
15. Positive for human immunodeficiency virus (HIV) antibody, active hepatitis B virus (HBV) infection, liver cirrhosis, or hepatitis C virus (HCV) infection;
16. Occurrence of severe infection within 4 weeks prior to the first dose of the investigational drug;
17. Presence of large-volume serous cavity effusion, or serous cavity effusion with significant symptoms;
18. Presence of lymphangitic carcinomatosis;
19. Receiving systemic corticosteroid therapy at a dose of > 10 mg/day prednisone or equivalent prior to randomization;
20. Presence of severe neurological or psychiatric disorders;
21. Clinically significant bleeding or obvious bleeding tendency within 4 weeks prior to signing informed consent;
22. Intestinal obstruction, Crohn's disease, ulcerative colitis, or chronic diarrhea, etc.;
23. Planned vaccination or receipt of live vaccine within 28 days prior to the first dose;
24. Presence of other severe physical conditions, laboratory abnormalities, or poor compliance, which may increase the risk of participating in the study, interfere with the study results, or render the patient unsuitable for enrollment as judged by the investigator.