BL-M07D1 versus T-DM1 after surgery for HER2‑positive breast cancer with residual invasive disease following neoadjuvant therapy

A Randomized Controlled Phase Ill Clinical Study of BL-M07D1 for Injection Versus Trastuzumab Emtansine (T-DM1) in the Adjuvant Treatment of HER2-positive Breast Cancer With Residual Invasive Cancer After Neoadjuvant Therapy

This trial will test whether BL‑M07D1 works better than T‑DM1 as additional treatment after surgery for people with HER2‑positive breast cancer who still have invasive cancer following pre-surgery therapy.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 1450 (estimated)
• Ages: 18 Years to 75 Years
• Sex: Female
• Sponsor: Sichuan Baili Pharmaceutical Co., Ltd. (Industry-sponsored)
• Drugs / interventions: immunotherapy, radiation, doxorubicin, prednisone
• Locations: 2 sites (Nanjing, Jiangsu and 1 other locations)
• Trial ID: NCT06830889 on ClinicalTrials.gov

What this trial studies

This is a randomized, open‑label, multicenter phase III trial comparing the antibody‑drug conjugate BL‑M07D1 to the approved agent T‑DM1 given as adjuvant therapy for patients with HER2‑positive breast cancer who have residual invasive disease after neoadjuvant treatment. Eligible patients are randomized after radical mastectomy, generally within 3 to 12 weeks of surgery, and must have good performance status and recovery from prior treatment. The trial will compare efficacy and safety outcomes, focusing on recurrence rates and treatment‑related adverse events. The study is sponsored by Sichuan Baili Pharmaceutical and is being conducted at multiple cancer centers in China.

Who should consider this trial

Good fit: Women aged 18–75 with histologically confirmed HER2‑positive invasive breast cancer who received neoadjuvant therapy, underwent radical mastectomy, have residual invasive disease on pathology, and have ECOG performance status 0–1 are the intended candidates.

Not a fit: Patients who achieved a pathological complete response after neoadjuvant therapy, have metastatic disease, or have poor performance status or unresolved high‑grade toxicity from prior treatment are unlikely to benefit from enrollment.

Why it matters

Potential benefit: If successful, BL‑M07D1 could lower the risk of cancer recurrence and improve long‑term outcomes compared with current adjuvant T‑DM1 for this high‑risk group.

How similar studies have performed: Previous phase III work in this setting (notably the KATHERINE trial) showed that T‑DM1 improved invasive disease‑free survival compared with trastuzumab, while BL‑M07D1 is a newer agent being directly compared against T‑DM1.

Eligibility criteria

Inclusion Criteria:

1. Sign the informed consent form voluntarily and follow the protocol requirements;
2. Women aged ≥18 years and ≤75 years at the time of written informed consent;
3. Expected survival time ≥6 months;
4. Patients with histologically confirmed HER2-positive invasive breast cancer;
5. Before neoadjuvant therapy, the clinical TNM staging was T1-4, N0-3, M0 (excluding T1N0) based on the 8th edition of the American Joint Committee on Cancer (AJCC) staging system;
6. The presence of residual invasive cancer confirmed by postoperative pathological examination must meet one of the conditions specified in the protocol;
7. Previous neoadjuvant therapy should meet the prescribed treatment conditions;
8. Had received radical mastectomy;
9. Determine hormone receptor (HR) status;
10. The interval between radical surgery and randomization was at least 3 weeks and at most 12 weeks;
11. ECOG score 0 or 1;
12. The toxicity of previous antineoplastic therapy has returned to ≤ grade 1 as defined by NCI-CTCAE v5.0;
13. No blood transfusion within 14 days before the first use of the study drug and no use of colony-stimulating factors were allowed;
14. For premenopausal women with childbearing potential, a pregnancy test must be performed within 7 days before starting treatment, serum pregnancy must be negative, and the patient must not be lactating; All enrolled patients should use adequate and highly effective contraception during the entire treatment cycle and for 7 months after the end of treatment.

Exclusion Criteria:

1. A diagnosis of stage IV metastatic breast cancer was made;
2. Bilateral breast cancer;
3. Any previous history of breast cancer (unilateral or contralateral) except for lobular carcinoma in situ (LCIS);
4. Evidence of clinically significant residual disease or recurrent or metastatic disease after neoadjuvant therapy and surgery;
5. Other primary malignancies diagnosed within 5 years before the first dose;
6. Received previous HER2-ADC, immunotherapy, or other antitumor biological therapy;
7. Subjects are participating in other clinical studies and receiving anti-tumor treatment;
8. Prior treatment with anthracyclines, doxorubicin equivalent cumulative dose \> 240 mg/m2; Cumulative dose of epirubicin or liposomal doxorubicin hydrochloride \> 480 mg/m2;
9. History of severe cardiovascular or cerebrovascular disease within six months before screening;
10. QT prolongation, complete left bundle branch block, III degree atrioventricular block, frequent and uncontrollable arrhythmia;
11. Poorly controlled hypertension (systolic blood pressure \> 150 mmHg or diastolic blood pressure \> 100 mmHg);
12. Complicated with pulmonary diseases leading to severe impairment of lung function;
13. A history of ILD/interstitial pneumonia requiring steroid therapy, current ILD/interstitial pneumonia, or suspected such disease during screening; CTCAE v5.0 was used to define grade ≥3 pulmonary disease and grade ≥2 radiation pneumonitis;
14. Human immunodeficiency virus antibody (HIVAb) positive, active hepatitis B virus infection, liver cirrhosis, or hepatitis C virus infection;
15. Had a serious infection within 4 weeks before the first dose of study drug; There was active pulmonary inflammation at the time of screening;
16. Were receiving \&gt within 2 weeks before the first dose; 10mg/d prednisone systemic corticosteroids or equivalent anti-inflammatory active drugs or any form of immunosuppressive therapy;
17. Patients with a history of severe allergy to recombinant humanized antibodies or to any of the excipents of BL-M07D1;
18. Known hypersensitivity or delayed hypersensitivity to certain components of T-DM1 or similar drugs, or known contraindications to T-DM1;
19. Had a history of autologous or allogeneic stem cell transplantation or organ transplantation;
20. Have a severe neurological or psychiatric illness;
21. Subjects with clinically significant bleeding or obvious bleeding tendency within 4 weeks before signing the informed consent;
22. Intestinal obstruction, Crohn's disease, ulcerative colitis or chronic diarrhea;
23. Subjects scheduled to receive live vaccine or within 28 days before the first dose;
24. Patients with other serious physical and laboratory abnormalities or poor adherence that may increase the risk of participating in the study, or interfere with the results of the study, and patients who were deemed by the investigators to be unsuitable for participation in the study.

Where this trial is running

Nanjing, Jiangsu and 1 other locations

• Jiangsu Province Hospital — Nanjing, Jiangsu, China (Recruiting)
• Fudan University Shanghai Cancer Center — Shanghai, Shanghai Municipality, China (Recruiting)

Study contacts

• Study coordinator: Sa Xiao, PHD

Conditions HER2-positive Breast Cancer; HER2-positive breast cancer with residual invasive cancer after neoadjuvant therapy