A Study of BL-B01D1 in Patients With Unresectable Locally Advanced or Metastatic Breast Cancer and Other Solid Tumors

A Phase I Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetic Characteristics and Preliminary Efficacy of BL-B01D1 in Patients With Unresectable Locally Advanced or Metastatic Breast Cancer and Other Solid Tumors

In this study, the dose-limiting toxicity (DLT), maximum tolerated dose (MTD), recommended phase II dose (RP2D), the preliminary efficacy, pharmacokinetic characteristics, and immunogenicity of BL-B01D1 will be investigated in patients with unresectable locally advanced or metastatic breast cancer and other solid tumors.

In phase Ia, the safety and tolerability of BL-B01D1 in patients with unresectable locally advanced or metastatic breast cancer and other solid tumors. investigated to determine the dose-limiting toxicity (DLT), and maximum tolerated dose (MTD) of BL-B01D1.

In phase Ib, the safety and tolerability of BL-B01D1 at the phase Ia recommended dose will be further investigated, and recommended phase II dose (RP2D) for phase II clinical studies will be determined The preliminary efficacy, pharmacokinetic characteristics, and immunogenicity of BL-B01D1 in patients with locally advanced or metastatic solid tumors will be evaluated.

EGFR and/or HER3 protein expression or gene amplification in tumor pathological tissues will be detected, and the expression of related ligand will be explored to study its correlation with the validity index of BL-B01D1, and the biomarkers will be optimized to further study the correlation between selected biomarkers and initial efficacy.

Inclusion Criteria:

1. Voluntarily sign the informed consent form and comply with the protocol requirements;
2. No gender restrictions;
3. Age: ≥18 years and ≤75 years;
4. Expected survival time ≥3 months;
5. Histologically and/or cytologically confirmed unresectable locally advanced or metastatic breast cancer and other solid tumors with failed standard treatment, intolerance to standard treatment, no current standard treatment available, or inability to access standard treatment;
6. Enrolled subjects should not have received prior systemic therapy for unresectable locally advanced or recurrent/metastatic triple-negative breast cancer;
7. Agree to provide archived tumor tissue specimens or fresh tissue samples from primary or metastatic lesions within the past 3 years;
8. Must have at least one measurable lesion as defined by RECIST v1.1;
9. ECOG performance status score of 0 or 1;
10. Toxicity from prior anti-tumor therapy has recovered to ≤ Grade 1 as defined by NCI-CTCAE v5.0;
11. No severe cardiac dysfunction, with left ventricular ejection fraction (LVEF) ≥50%;
12. Organ function levels must meet the requirements without transfusion or use of any cell growth factors and/or platelet-raising drugs within 14 days before the first dose of the study drug;
13. Coagulation function: International Normalized Ratio (INR) ≤1.5, and activated partial thromboplastin time (APTT) ≤1.5 × ULN;
14. Urine protein ≤2+ or ≤1000 mg/24h;
15. For premenopausal women with childbearing potential, a pregnancy test (serum or urine) must be performed within 7 days before starting treatment, and the result must be negative; they must not be breastfeeding. All enrolled patients (regardless of gender) must use adequate barrier contraception throughout the treatment period and for 6 months after treatment ends.

Exclusion Criteria:

1. Received biological therapy, immunotherapy, or other antitumor treatments within 4 weeks or 5 half-lives prior to the first dose (6 weeks for mitomycin and nitrosoureas; oral fluorouracil drugs such as tegafur/gimeracil/oteracil (S-1) or capecitabine, or oral endocrine therapy, or palliative radiotherapy within 2 weeks before the first dose);
2. History of severe heart disease;
3. Prolonged QT interval, complete left bundle branch block, third-degree atrioventricular block, or severe arrhythmia;
4. Active autoimmune or inflammatory diseases;
5. Diagnosis of other malignancies within 2 years prior to the first dose;
6. Poorly controlled hypertension (systolic blood pressure >150 mmHg or diastolic blood pressure >100 mmHg) despite the use of two antihypertensive medications;
7. Poorly controlled blood glucose (defined as: a) two fasting blood glucose levels >10 mmol/L, or b) glycated hemoglobin level exceeding 8%), or concurrent diabetic gangrene;
8. History of interstitial lung disease (ILD), current ILD, or suspected ILD based on imaging during screening;
9. Concurrent pulmonary disease leading to clinically significant respiratory impairment;
10. Unstable deep vein thrombosis, arterial thrombosis, pulmonary embolism, or other thrombotic events requiring therapeutic intervention within 6 months before screening (excluding catheter-related thrombosis);
11. Patients with central nervous system (CNS) metastases and/or carcinomatous meningitis (leptomeningeal metastases);
12. Patients with significant serous cavity effusion, symptomatic effusion, or poorly controlled effusion;
13. History of hypersensitivity to recombinant humanized antibodies or human-mouse chimeric antibodies, or any excipients of BL-B01D1;
14. Imaging findings indicating tumor invasion or encasement of major thoracic, cervical, or pharyngeal blood vessels, unless the investigator deems it does not affect the patient's eligibility for treatment;
15. Previous organ transplantation or allogeneic hematopoietic stem cell transplantation (Allo-HSCT);
16. Cumulative anthracycline dose >360 mg/m² in prior (neo)adjuvant anthracycline therapy;
17. Positive for human immunodeficiency virus antibody (HIVAb), active tuberculosis, active hepatitis B virus (HBV) infection, or active hepatitis C virus (HCV) infection;
18. Severe infection (CTCAE > Grade 2) within 4 weeks before the first dose of the study drug; signs of active pulmonary infection within 2 weeks before the first dose;
19. Participation in another clinical trial within 4 weeks before the first dose (calculated from the last dose date);
20. Any other condition deemed unsuitable for participation in this clinical trial by the investigator.