Overview

This study is an open-label, multicenter, dose-escalation and cohort-expansion, non-randomized Phase I clinical trial to evaluate the safety, tolerability, pharmacokinetic characteristics, and preliminary efficacy of BL-M09D1 for injection in patients with locally advanced or metastatic non-small cell lung cancer and other solid tumors.

Eligibility

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 (Phase Ia); ≥18 years (Phase Ib);
4. Expected survival time ≥3 months;
5. Histologically or cytologically confirmed locally advanced or metastatic non-small cell lung cancer or other solid tumors that have failed standard treatment;
6. Willing to provide archived or fresh tumor tissue samples from primary or metastatic lesions within the past 2 years;
7. Must have at least one measurable lesion as defined by RECIST v1.1;
8. ECOG performance status score of 0 or 1;
9. Toxicities from prior anti-tumor therapy have recovered to ≤ Grade 1 as defined by NCI-CTCAE v5.0;
10. No severe cardiac dysfunction, left ventricular ejection fraction (LVEF) ≥50%;
11. Organ function levels must meet the requirements;
12. Coagulation function: International Normalized Ratio (INR) ≤1.5, and activated partial thromboplastin time (APTT) ≤1.5 × upper limit of normal (ULN);
13. Urine protein ≤2+ or ≤1000mg/24h;
14. For premenopausal women with childbearing potential, a serum pregnancy test must be negative within 7 days before starting treatment, and 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 completion;
15. The subject has the ability and willingness to comply with the visits, treatment plans, laboratory tests, and other study-related procedures specified in the protocol.

Exclusion Criteria:

1. Received chemotherapy, biological therapy, immunotherapy, etc., within 4 weeks or 5 half-lives before the first dose;
2. History of severe cardiac disease;
3. Prolonged QT interval, complete left bundle branch block, or third-degree atrioventricular block;
4. Active autoimmune or inflammatory diseases;
5. Diagnosed with another malignancy within 5 years before the first dose (except cured basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ of the cervix);
6. Unstable thrombotic events requiring therapeutic intervention within 6 months before the first dose;
7. Poorly controlled hypertension;
8. Poorly controlled diabetes mellitus;
9. History of interstitial lung disease (ILD) requiring steroid therapy, current ILD, or ≥Grade 2 radiation pneumonitis;
10. Concurrent pulmonary diseases resulting in clinically severe respiratory impairment;
11. Active central nervous system metastases;
12. History of allergy to recombinant humanized antibodies or human-mouse chimeric antibodies, or hypersensitivity to any excipient of BL-M09D1;
13. Previous organ transplantation or allogeneic hematopoietic stem cell transplantation (Allo-HSCT);
14. Cumulative dose of anthracyclines >360 mg/m² in prior (neo)adjuvant anthracycline therapy;
15. Positive for human immunodeficiency virus (HIV) antibody, active tuberculosis, active hepatitis B virus (HBV) infection, or active hepatitis C virus (HCV) infection;
16. Active infections requiring systemic treatment within 4 weeks before the first study drug administration;
17. Pleural, peritoneal, pelvic, or pericardial effusion requiring drainage and/or symptomatic within 4 weeks before the first study drug administration;
18. Participation in another clinical trial within 4 weeks or 5 half-lives before the first dose;
19. Pregnant or lactating women;
20. Other conditions deemed by the investigator as unsuitable for participation in this clinical trial.