A Study of BL-B01D1 in Patients With Locally Advanced or Metastatic Solid Tumor

A Phase I Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetic Characteristics and Preliminary Efficacy of BL-B01D1 in Patients With Locally Advanced or Metastatic Solid Tumor

In phase Ia study, the safety and tolerability of BL-B01D1 in patients with locally advanced or metastatic solid tumor will be investigated to determine the dose-limiting toxicity (DLT), maximum tolerated dose (MTD) of BL-B01D1.

In phase Ib study, the safety and tolerability of BL-B01D1 at the phase Ia recommended dose will be further investigated, and recommended phase II dose (RP2D) for phase II clinical studies will be determined.

In addition, the preliminary efficacy, pharmacokinetic characteristics, and immunogenicity of BL-B01D1 in patients with locally advanced or metastatic solid tumor will be evaluated.

Inclusion Criteria:

1. Participants must sign the informed consent form voluntarily and follow the plan requirements.
2. No gender limit.
3. Age: ≥18 years old and ≤75 years old (stage Ia); ≥18 years old (stage Ib).
4. Expected survival time ≥ 3 months.
5. Locally advanced or metastatic solid tumor confirmed by histopathology and/or cytology, which are incurable or currently without standard treatment.
6. Agrees to provide archived tumor tissue specimens or fresh tissue samples from the primary lesion or metastasis within 2 years; If a subject is unable to provide a tumor tissue sample, he/she may be enrolled after being evaluated by the investigator if other inclusion criteria are met.
7. Participants must have at least one measurable lesion that meets the definition of RECIST v1.1.
8. Physical fitness score ECOG 0 or 1 point
9. 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, such as hair loss and grade 2 peripheral neurotoxicity, were excluded. Or decreased hemoglobin except ≥90 g/L).
10. No serious cardiac dysfunction, left ventricular ejection fraction (LVEF) ≥50%
11. The organ function level must meet the following requirements: a) bone marrow function: absolute neutrophilic granulocyte count (ANC) ≥1.5×109/L, platelet count ≥90×109/L, hemoglobin ≥90 g/L; b) Liver function: total bilirubin (TBIL≤1.5 ULN), AST and ALT ≤2.5 ULN in patients without liver metastasis, AST and ALT ≤5.0 ULN in patients with liver metastasis; c) Kidney function: creatinine (Cr) ≤1.5 ULN, or creatinine clearance (Ccr) ≥50 mL/min (according to Cockcroft and Gault formula).
12. Coagulation function: International normalized ratio (INR)≤1.5×ULN, 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 taken within 7 days prior to the start of treatment. Serum or urine pregnancy must be negative and must be non-lactating; all participants (regardless of male or female) in the group should be treated throughout the treatment. Adequate barrier contraceptive measures should be taken during the treatment and 6 months after the treatment.

Exclusion Criteria:

1. Chemotherapy, biological therapy, immunotherapy, radical radiotherapy, major surgery, targeted therapy (including small molecule inhibitor of tyrosine kinase), and other anti-tumor therapy within 4 weeks or 5 half-lives (whichever is shorter) prior to the first administration; mitomycin and nitrosoureas treatment within 6 weeks prior to the first administration; oral fluorouracil-like drugs such as S-1, capecitabine, or palliative radiotherapy within 2weeks prior to the first administration.
2. 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.
3. Participants with prolonged QT interval (male QTc> 450 msec or female QTc> 470 msec), complete left bundle branch block, III grade atrioventricular block.
4. 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).
5. Other malignant tumors were diagnosed within 5 years prior to the first administration with the following exceptions: basal cell carcinoma of the skin, squamous cell carcinoma of the skin and/or carcinoma in situ after radical resection.
6. Participants with poorly controlled hypertension by two kinds of antihypertensive drugs (systolic blood pressure>150 mmHg or diastolic blood pressure>100 mmHg).
7. Participants have grade 3 lung disease defined according to NCI-CTCAE v5.0, or a history of interstitial lung disease (ILD).
8. 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.
9. Symptoms of active central nervous system metastasis. However, patients with stable brain parenchymal metastases can be enrolled. Stable was defined as: a. The seizure-free state lasted for > 12 weeks with or without the use of antiepileptic drugs; b. Glucocorticoid use is not required; c. Consecutive MRI scans (at least 8 weeks between scans) showed stable imaging status.
10. Patients with a history of allergy to recombinant humanized antibody or mouse chimeric antibody or to any excipients of BL-B01D1.
11. Previous recipients of organ transplantation or allogeneic hematopoietic stem cell transplantation (Allo-HSCT).
12. In previous adjuvant therapy with anthracyclines, the cumulative dose of anthracyclines was > 360 mg/m2.
13. Positive human immunodeficiency virus antibody (HIVAb), active tuberculosis, active hepatitis B virus infection (HBV-DNA copy number > 103 IU/ml) or active hepatitis C virus infection (HCV antibody positive and HCV-RNA > lower limit of detection).
14. Active infections requiring systemic treatment, such as severe pneumonia, bacteremia, septicemia, etc.
15. Participated in another clinical trial (calculated from the time of the last dose) within 4 weeks prior to the first dose.
16. The other conditions of participation in this clinical trial were not considered appropriate by the investigators.