Phase I Clinical Study of BL-M07D1 in Locally Advanced or Metastatic Digestive Tract Tumors and Other Solid Tumors

Exclusion Criteria

• •1. Antitumor therapy such as chemotherapy, biotherapy, immunotherapy, radical radiotherapy, major surgery, targeted therapy (including small-molecule tyrosine kinase inhibitors) within 4 weeks prior to initial administration or within 5 half-lives, whichever is shorter; Mitomycin and nitrosourea were administered within 6 weeks before the first administration. Oral fluorouracil drugs such as Tizio, capecitabine, or palliative radiotherapy within 2 weeks prior to initial administration; Traditional Chinese medicines or proprietary Chinese medicines with anti-tumor indications should be administered within 2 weeks before the first administration.
• •2. Previously received ADC drug therapy with camptothecin derivatives (topoisomerase I inhibitors) as toxins (Phase Ib only).
• •3. History of severe heart disease, such as symptomatic congestive heart failure (CHF) ≥2 (CTCAE 5.0), New York Heart Society (NYHA) ≥2 heart failure, history of transmural myocardial infarction, unstable angina, etc.
• •4. Prolonged QT interval (QTcF \> 450 msec in men or 470 msec in women), complete left bundle branch block, and degree III atrioventricular block.
• •5. Active autoimmune or inflammatory diseases, such as systemic lupus erythematosus, psoriasis requiring systemic treatment, rheumatoid arthritis, inflammatory bowel disease, and Hashimoto's thyroiditis, other than type I diabetes, hypothyroidism that can be controlled by alternative therapy alone, skin diseases that do not require systemic treatment (e.g., vitiligo, psoriasis).
• •6. Other malignancies developed within 3 years of enrollment, excluding:(1)radical cervical carcinoma in situ or non-melanoma skin cancer;(2)the second primary cancer that has been completely cured and no recurrence within 3 years;(3)The researchers believed that both primary cancers could benefit from this study;(4)The investigators have clearly ruled out which primary tumor source the metastases belong to.
• •7. Unstable thrombotic events such as deep vein thrombosis, arterial thrombosis, and pulmonary embolism requiring therapeutic intervention within 6 months prior to screening; Thrombus formation associated with infusion set is excluded.
• •8. The poorly controlled pericardial effusion, pleural effusion and abdominal effusion with clinical symptoms were not suitable for inclusion by the researchers.
• •9. Hypertension poorly controlled by antihypertensive medications (systolic blood pressure \> 150 mmHg or diastolic blood pressure \> 100 mmHg).
• •10. According to CTCAE v5.0, patients were defined as ≥3 lung disease, ≥2 radiation lung disease, present or history of interstitial lung disease (ILD).
• •11. Patients who received lung radiation therapy within 6 months with total dose ≥30 Gy.
• •12. Patients with active central nervous system metastases. But the researchers believe that patients with stable brain parenchymal metastases can be included. The definition of stability should meet the following four requirements:
• •1. Seizures-free status lasting \> 12 weeks with or without antiepileptic medication;
• •2. No need for glucocorticoids;
• •3. Two consecutive MRI scans (scan interval at least 4 weeks) showed stable imaging status;
• •4. Asymptomatic patients stable for more than 1 month after treatment.
• •13. Patients with a history of allergy to recombinant humanized antibodies or human and mouse chimeric antibodies or to any excipient component of BL-M07D1.
• •14. Previous recipients of organ transplantation or allogeneic hematopoietic stem cell transplantation (Allo-HSCT).
• •15. In previous treatment with anthracyclines, the equivalent cumulative dose of doxorubicin was greater than 360 mg/m2.
• •16. Human immunodeficiency virus antibody (HIVAb) positive, active tuberculosis, active hepatitis B virus infection (HBV-DNA copy number \> lower limit of detection) or active hepatitis C virus infection (HCV antibody positive and HCV-RNA \> lower limit of detection).
• •17. Active infections requiring systemic treatment, such as severe pneumonia, bacteremia, sepsis, etc.
• •18. Had participated in another clinical trial within 4 weeks prior to the first dose (counting from the time of the last dose).
• •19. A pregnant or nursing woman.
• •20. Other conditions included in this clinical trial were not considered appropriate.