A Study of BL-M24D1 in Patients With Locally Advanced or Metastatic Gastrointestinal Tumors and Other Solid Tumors

A Phase I Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetic Characteristics and Preliminary Efficacy of BL-M24D1 for Injection in Patients With Locally Advanced or Metastatic Gastrointestinal Tumors and Other Solid Tumors

This study is an open, multicenter, non-randomized phase I clinical trial to evaluate the safety, tolerability, pharmacokinetic characteristics and preliminary efficacy of BL-M24D1 for Injection in patients with locally advanced or metastatic gastrointestinal tumors and other solid tumors.

The study is divided into two phases: a dose escalation phase (Phase Ia) and a cohort expansion phase (Phase Ib).

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. Locally advanced or metastatic digestive tract tumors and other solid tumors;
6. Agree to provide archived tumor tissue specimens or fresh tissue samples from primary or metastatic lesions within the past 3 years;
7. Must have at least one measurable lesion meeting the RECIST v1.1 criteria;
8. ECOG performance status score of 0 or 1;
9. Toxicities from prior antitumor treatments have recovered to ≤ Grade 1 as defined by NCI-CTCAE v5.0;
10. No severe cardiac dysfunction, left ventricular ejection fraction ≥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 × ULN;
13. Urine protein ≤2+ or ≤1000mg/24h;
14. For premenopausal women with childbearing potential, a pregnancy test must be conducted within 7 days before starting treatment, serum pregnancy must be negative, and they must not be breastfeeding; all enrolled patients (regardless of gender) should adopt adequate barrier contraception throughout the treatment cycle and for 6 months after treatment ends.

Exclusion Criteria:

1. Use of chemotherapy, biological therapy, or immunotherapy within 4 weeks prior to the first dose or within 5 half-lives;
2. History of severe heart disease;
3. QT interval prolongation, complete left bundle branch block, or third-degree atrioventricular block;
4. Active autoimmune or inflammatory diseases;
5. Diagnosis of other malignancies within 5 years prior to the first dose;
6. Hypertension poorly controlled by two antihypertensive medications;
7. Patients with poorly controlled blood glucose;
8. Unstable thrombotic events requiring therapeutic intervention within 6 months prior to the first dose;
9. Lung diseases graded ≥3 according to CTCAE v5.0;
10. Symptoms of active central nervous system metastases;
11. History of allergy to recombinant humanized antibodies or human-mouse chimeric antibodies, or allergy to any excipient component of BL-M24D1;
12. Previous organ transplantation or allogeneic hematopoietic stem cell transplantation (Allo-HSCT);
13. Cumulative dose of anthracyclines >360 mg/m² in previous (neo)adjuvant anthracycline therapy;
14. Human immunodeficiency virus antibody positivity, active tuberculosis, active hepatitis B virus infection, or active hepatitis C virus infection;
15. History of interstitial lung disease (ILD) requiring steroid treatment, or current ILD;
16. Active infection requiring systemic treatment within 4 weeks prior to the first investigational drug dose;
17. Pleural, abdominal, pelvic, or pericardial effusion requiring drainage and/or accompanied by symptoms within 4 weeks prior to the first investigational drug dose;
18. Subjects with clinically significant bleeding or obvious bleeding tendency within 4 weeks prior to the first investigational drug dose;
19. Participation in another clinical trial within 4 weeks prior to the first dose;
20. Pregnant or lactating women;
21. Other conditions deemed by the investigator as unsuitable for participation in this clinical trial.