Overview

This study is an open, multicenter, increasing dose and dose extension nonrandomized phase I clinical study to evaluate the safety, tolerability, pharmacokinetics characteristics and preliminary efficacy of BL-B16D1 in patients with unresectable locally advanced or metastatic breast cancer and other solid tumor.

Eligibility

Inclusion Criteria:

1. Sign the informed consent form voluntarily and follow the protocol requirements;
2. Gender is not limited;
3. Age: ≥18 years old and ≤75 years old (stage Ia); ≥18 years old (stage Ib);
4. Expected survival time ≥3 months;
5. Patients with histologically and/or cytologically confirmed unresectable locally advanced or metastatic breast cancer and other solid tumors who failed or could not receive standard treatment;
6. Consent to provide archival tumor tissue samples or fresh tissue samples from primary or metastatic lesions within 3 years;
7. Must have at least one extracranial measurable lesion that meets the RECIST v1.1 definition;
8. ECOG 0 or 1;
9. The toxicity of previous antineoplastic therapy has returned to ≤ grade 1 as defined by NCI-CTCAE v5.0;
10. No severe cardiac dysfunction, left ventricular ejection fraction ≥50%;
11. The organ function level must meet the requirements if the patient has not received blood transfusion or hematopoietic stimulation factor therapy within 14 days before the first dose;
12. Coagulation function: international normalized ratio ≤1.5, and activated partial thromboplastin time ≤1.5ULN;
13. Urinary protein ≤2+ or ≤1000mg/24h;
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 (male or female) should use adequate contraception throughout the treatment cycle and for 6 months after completion of treatment.

Exclusion Criteria:

1. Chemotherapy, biological therapy and other anti-tumor therapies have been used within 4 weeks or 5 half-lives before the first dose; Mitomycin and nitrosoureas were administered within 6 weeks before the first dose; Oral drugs such as fluorouracil;
2. History of severe heart disease;
3. Prolonged QT interval, complete left bundle branch block, III degree atrioventricular block;
4. Active autoimmune and inflammatory diseases;
5. Patients with other malignant tumors or a history of other malignant tumors;
6. Unstable thrombotic events requiring therapeutic intervention within 6 months before screening; Infusion-related thrombosis was excluded;
7. Hypertension poorly controlled by two antihypertensive drugs (systolic blood pressure > 150 mmHg or diastolic blood pressure > 100 mmHg);
8. Patients with poor glycemic control;
9. Patients with grade ≥1 radiation pneumonitis according to the RTOG/EORTC definition; Previous history of ILD or current ILD, or suspicion of such disease during screening;
10. Complicated with pulmonary diseases leading to clinically severe respiratory function impairment;
11. Patients with primary central nervous system (CNS) tumors or CNS metastases that had failed local treatment;
12. Patients with a history of allergy to recombinant humanized antibody or human-mouse chimeric antibody or to any of BL-B16D1's excipients;
13. Received previous organ transplantation or allogeneic hematopoietic stem cell transplantation (Allo-HSCT);
14. In previous (new) adjuvant anthracyclines, the cumulative dose of anthracyclines for doxorubicin > 550 mg/m2, epirubicin > 900 mg/m2 or the equivalent dose of other similar drugs;
15. Human immunodeficiency virus antibody positive, active tuberculosis, active hepatitis B virus infection or active hepatitis C virus infection;
16. Serious infection occurred within 4 weeks before the first dose; Signs of pulmonary infection or active pulmonary inflammation within 2 weeks before the first dose;
17. Patients with massive or symptomatic effusions, or poorly controlled effusions;
18. Had participated in another clinical trial within 4 weeks before the first dose (calculated from the time of the last dose);
19. Had the following eye diseases: a. active infection or corneal ulcer; b. monocular vision; c. a history of corneal transplantation; d. Contact lens dependence; e. Uncontrolled glaucoma; f. Uncontrolled or progressive retinopathy, wet macular degeneration, etc.;
20. Other circumstances that the investigator deemed inappropriate for participation in the trial.