A Study of BL-M02D1 in Patients With Locally Advanced or Metastatic Triple Negative Breast Cancer or Other Solid Tumors

Prior treatment

• Antitumor therapy such as chemotherapy, biotherapy, immunotherapy, radical radiotherapy, major surgery (as defined by the investigators), and 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 before first administration; Traditional Chinese medicines with anti-tumor indications were administered within 2 weeks before the first dose.
• Prior treatment with ADC drugs targeting TROP2 or ADC drugs using camptothecin derivatives (topoisomerase I inhibitors) as toxins.
• The presence of a second primary tumor within 5 years prior to initial administration, except for radical basal cell carcinoma of the skin, squamous cell carcinoma of the skin, and/or radical resected carcinoma in situ.
• There are symptoms of active central nervous system metastasis. However, the researchers concluded that patients with stable brain parenchymal metastases could be included. Stable is defined as: a. The seizureless state persists for \> 12 weeks with or without antiepileptic medication; b. Glucocorticoid use is not required; c. Two consecutive MRI scans (at least 4 weeks between scans) showed stable imaging status; d. Asymptomatic patients stable for more than 1 month after treatment.
• Participated in another clinical trial within 4 weeks prior to participating in the study.

Other illness

• Patients screened for any of the following conditions will not be included in this study:
• Participants with history of severe heart disease, such as: symptomatic congestive heart failure (CHF) ≥ grade 2 (CTCAE 5.0), New York Heart Association (NYHA) ≥ grade 2 heart failure, history of transmural myocardial infarction, unstable angina pectoris etc.
• Active autoimmune diseases and inflammatory diseases, such as: systemic lupus erythematosus, psoriasis requiring systemic treatment, rheumatoid arthritis, inflammatory bowel disease and Hashimoto's thyroiditis, etc., except for type I diabetes, hypothyroidism that can be controlled only by alternative treatment, and skin diseases that do not require systemic treatment (such as vitiligo, psoriasis).
• Screening for unstable thrombotic events such as deep vein thrombosis, arterial thrombosis and pulmonary embolism requiring therapeutic intervention within the first 6 months; Infusion device-related thrombosis is excluded;
• Participants with poorly controlled hypertension by antihypertensive drugs (systolic blood pressure\>150 mmHg or diastolic blood pressure\>100 mmHg).
• Lung disease defined as grade ≥3 according to CTCAE V5.0; ≥2 grade of radioactive lung disease, current or history of interstitial lung disease (ILD).
• Participants who have a history of allergies to recombinant humanized antibodies or human-mouse chimeric antibodies or any of the components of BL-M02D1.
• Participants have a history of organ transplantation or allogeneic stem cell transplantation (Allo-HSCT).
• Human immunodeficiency virus antibody (HIVAb) positive, active tuberculosis, active hepatitis B virus infection (HBV-DNA copy number\> the lower limit of detection) or active hepatitis C virus infection (HCV antibody positive and HCV-RNA \> the lower limit of detection).
• Participants with active infections requiring systemic treatment, such as severe pneumonia, bacteremia, sepsis, etc.
• Other conditions that the investigator believes that it is not suitable for participating in this clinical trial.

Lab values

• Participants with prolonged QT interval (male QTc\> 450 msec or female QTc\> 470 msec), complete left bundle branch block, III grade atrioventricular block.

Other

• Patients with poorly controlled pleural effusion with clinical symptoms were judged by researchers to be unsuitable for inclusion.
• In the adjuvant (or neoadjuvant) treatment of anthracyclines, the cumulative dose of anthracyclines is\> 360 mg/m2.
• Pregnant or nursing women.

• Participants must sign the informed consent form voluntarily and follow the plan requirements.
• No gender limit.
• Age: ≥18 years old and ≤75 years old (phase Ia); ≥18 years old (phase Ib).
• Expected survival time ≥ 3 months.
• Locally advanced or metastatic gastrointestinal tumor and other solid tumor confirmed by histopathology and/or cytology, which are incurable or currently without standard treatment.
• Participants must agree to provide archived tumor tissue specimens or fresh tissue samples of the primary tumor or metastasis; if the participant is unable to provide tumor tissue samples, the investigator will evaluate whether the participant could be enrolled if other criteria are fit to join the group.
• Participants must have at least one assessable lesion in phase Ia; participants must have at least one measurable lesion that meets the definition of RECIST v1.1 in phase Ib.
• Has an Eastern Cooperative Oncology Group performance status (ECOG PS) 0-1
• Toxicity of previous antitumor therapy has returned to ≤ level 1 as defined by NCI-CTCAE v5.0 (except for asymptomatic laboratory abnormalities considered by the investigators, such as elevated ALP, hyperuricemia, and elevated blood glucose; Toxicities with no safety risk were excluded, such as alopecia, hyperpigmentation, and grade 2 peripheral neurotoxicity. Or except decreased hemoglobin but ≥90 g/L).
• Has adequate organ function before registration, defined as: a) Bone marrow function: Absolute neutrophil count (ANC) ≥1.5×109/L, Platelet count ≥100×109/L, Hemoglobin ≥90 g/L; B) Hepatic function: Total bilirubin (TBIL≤1.5 ULN), AST and ALT ≤2.5 ULN for participants without liver metastasis, AST and ALT ≤5.0 ULN for liver metastases; c) Renal function: Creatinine (Cr) ≤1.5 ULN, or creatinine clearance (Ccr) ≥50 mL/min (according to the Cockcroft and Gault formula).
• Coagulation function: International normalized ratio (INR)≤1.5×ULN, and activated partial thromboplastin time (APTT)≤1.5ULN.
• Urinary protein ≤2+ or ≤1000mg/24h.
• For premenopausal women with childbearing potential, a pregnancy test must be taken within 7 days prior to the start of treatment. Serum or urine pregnancy must be negative and must be non-lactating. Adequate barrier contraceptive measures should be taken during the treatment and 6 months after the end of treatment for all participants (regardless of male or female).