A Study of BL-M08D1 in Patients With Locally Advanced or Metastatic Solid Tumors

A Phase I Study to Evaluate the Safety, Tolerability, Pharmacokinetic Characteristics and Preliminary Efficacy of BL-M08D1 for Injection in Patients With Locally Advanced or Metastatic Solid Tumors

This study is an open, multicenter, dose-escalation and expansion-enrollment, nonrandomized phase I clinical study to evaluate the safety, tolerability, pharmacokinetic characteristics and preliminary efficacy of BL-M08D1 for injection 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 are incurable or currently have no standard treatment;
6. Consent to provide archival tumor tissue samples or fresh tissue samples from primary or metastatic lesions within 2 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. No blood transfusion, no use of cell growth factors and/or platelet-raising drugs within 14 days before screening, and the organ function level must meet the requirements;
12. Coagulation function: international normalized ratio (INR) ≤1.5, and activated partial thromboplastin time (APTT) ≤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 (regardless of male or female) should use adequate barrier contraception during the whole treatment cycle and for 6 months after the end of treatment;
15. Subjects were able and willing to comply with protocol-specified visits, treatment plans, laboratory tests, and other study-related procedures.

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. QT prolongation, complete left bundle branch block, III degree atrioventricular block;
4. Active autoimmune and inflammatory diseases;
5. Other malignant tumors diagnosed within 5 years before the first dose;
6. Hypertension poorly controlled by two antihypertensive drugs (systolic blood pressure > 150 mmHg or diastolic blood pressure > 100 mmHg);
7. History of ILD requiring steroid therapy or current ILD or ≥ grade 2 radiation pneumonitis;
8. Complicated with pulmonary diseases leading to clinically severe respiratory function impairment;
9. Had symptoms of active central nervous system metastasis;
10. Patients with a history of allergy to recombinant humanized antibody or human-mouse chimeric antibody or to any of the ingredients of BL-M08D1;
11. Received previous organ transplantation or allogeneic hematopoietic stem cell transplantation (Allo-HSCT);
12. Human immunodeficiency virus antibody positive, active tuberculosis, active hepatitis B virus infection or active hepatitis C virus infection;
13. Active infection requiring systemic therapy within 4 weeks before the first dose of study drug;
14. Pleural, abdominal, pelvic or pericardial effusion requiring drainage and/or with symptoms within 4 weeks before the first dose of study drug;
15. Received another trial drug 4 weeks or 5 half-lives before the first dose;
16. Pregnant or lactating women;
17. The investigator did not consider it appropriate to apply other criteria for participation in the trial.