A Study of BL-B16D1 in Patients With Locally Advanced or Metastatic Solid Tumors

A Phase I Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics Characteristics and Preliminary Efficacy of BL-B16D1 in Patients With Locally Advanced or Metastatic Solid Tumors

This study is an open, multicenter, dose-escalation and expansion-enrollment and nonrandomized phase I clinical study to evaluate the safety, tolerability, pharmacokinetic characteristics and preliminary efficacy of BL-B16D1 in locally advanced or metastatic solid tumors.

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 (phase Ia); ≥18 years old (phase Ib);
4. Expected survival time ≥3 months;
5. locally advanced or metastatic solid tumors confirmed by histopathology and/or cytology that failed standard treatment or could not obtain standard treatment;
6. Consent to provide archival tumor tissue samples or fresh tissue samples from primary or metastatic lesions within 3 years;
7. At least one measurable lesion meeting the RECIST v1.1 definition was required;
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 stimulating factor therapy within 14 days before screening;
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. Long QT, complete left bundle branch block, III degree atrioventricular block;
4. Active autoimmune and inflammatory diseases;
5. Other malignancies diagnosed within 5 years before the first dose;
6. Hypertension poorly controlled by two antihypertensive drugs;
7. Patients with poor glycemic control;
8. Present with grade ≥2 radiation pneumonitis according to the RTOG/EORTC definition; Previous history of ILD or current ILD, or suspicion of such disease during screening;
9. Complicated with pulmonary diseases leading to clinically severe respiratory function impairment;
10. Active central nervous system metastasis;
11. Patients with a history of allergy to recombinant humanized or human-mouse chimeric antibodies or to any of the excipients of BL-B16D1;
12. Received previous organ transplantation or allogeneic hematopoietic stem cell transplantation (Allo-HSCT);
13. The cumulative dose of anthracyclines > 360 mg/m2 in previous (new) adjuvant therapy;
14. Human immunodeficiency virus antibody positive, active tuberculosis, active hepatitis B virus infection or active hepatitis C virus infection;
15. Severe infection occurred within 4 weeks before the first dose; Signs of pulmonary infection or active pulmonary inflammation within 2 weeks before the first dose;
16. Patients with massive or symptomatic effusions or poorly controlled effusions;
17. Had participated in another clinical trial within 4 weeks before the first dose;
18. Had the following ocular 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.;
19. Other circumstances that the investigator deemed inappropriate for participation in the trial.