Locally advanced or metastatic solid tumors
Conditions
Interventions
Experimental group:Phase Ia
BL-B01D1 is administered via intravenous infusion, with the following cohorts designed:
Cohort A: Administered on Day 1 (D1) and Day 8 (D8), with a 3-week treatment cycle
Cohort B: Administered on Day 1 (D1), with a 3-week treatment cycle.
The infusion duration for the first dose is 120 minutes ± 10 minutes. If the infusion reaction is tolerable during the first admini
Sponsors
Sun Yat-sen University Cancer Center
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. Voluntarily sign the informed consent form and follow the requirements of the plan; 2. Gender is not limited; 3. Age: = 18 years old and = 75 years old; 4. Expected survival time: >=3 months; 5. Locally advanced or metastatic solid tumors that have been confirmed by histopathology and/or cytology and are incurable or currently have no standard treatment; 6. Agree to provide archived tumor tissue specimens or fresh tissue samples from the primary lesion or metastatic lesion within two years; If the subjects are unable to provide tumor tissue samples and meet other inclusion and exclusion criteria, they can be enrolled after evaluation by the researchers. 7. There must be at least one measurable lesion that conforms to the definition of RECIST v1.1; 8. Physical condition score ECOG: 0 or 1 point; 9. The toxicity of previous anti-tumor treatments has been restored to grade =90 g/L); 10. No serious cardiac function abnormalities, left ventricular ejection fraction >=50%; 11. Under the condition that blood transfusion and the use of any cell growth factors and/or platelet-raising drugs are not allowed within 14 days before the screening period examination, the organ function level must meet the following requirements and reach the following standards: a) Bone marrow function: Absolute neutrophil count (ANC) >=1.5×10^9/L, platelet count >=90×10^9/L, hemoglobin >=90 g/L; b) Liver function: Total bilirubin (TBIL<=1.5 ULN). For those without liver metastasis, both AST and ALT <=2.5 ULN; for those with liver metastasis, both AST and ALT <=5.0 ULN. c) Renal function: Creatinine (Cr) = 1.5 ULN, or creatinine clearance rate (Ccr) = 50 mL/min (according to the Cockcroft and Gault formula). 12. Coagulation function: International normalized ratio (INR) <=1.5, and activated partial thromboplastin time (APTT) <=1.5ULN; 13. Urine protein <=2+ or <=1000mg/24h; 14. For premenopausal women who have the potential to conceive, a pregnancy test must be conducted within 7 days before the start of treatment. The serum or urine pregnancy test must be negative and it must be a non-lactating period. All enrolled patients (regardless of gender) should take adequate barrier contraceptive measures throughout the treatment cycle and for 6 months after the end of treatment. Participants in cohorts 2 to 14 need to meet the following inclusion criteria: 15. Histologically or cytologically confirmed driver gene mutations other than classical EGFR mutations (non-classical EGFR mutations such as 20ins, 18exonG719X, 20exonS768I, 21exonL861Q, etc.), ALK fusions, ROS1 fusions, BRAF V600E Locally advanced or metastatic non-small cell lung cancer with mutations, NTRK fusions, MET exon 14 skipping mutations, RET fusions, KRAS G12C mutations, HER2 mutations, and SMARCA4 deletions; 16. Disease progression occurred after previous targeted therapy or systemic chemotherapy targeting the corresponding driver gene mutation.
Exclusion criteria
Exclusion criteria: Exclusion Criteria: 1. Received anti-tumor treatments such as chemotherapy, biological therapy, immunotherapy, radical radiotherapy, major surgery (as defined by the investigator), or targeted therapy (including small-molecule tyrosine kinase inhibitors) within 4 weeks or 5 half-lives (whichever is shorter) before the first dose; for mitomycin and nitrosourea drugs, this period is within 6 weeks before the first dose; for oral fluoropyrimidine drugs (e.g., tegafur-gimeracil-oteracil potassium, capecitabine) or palliative radiotherapy, this period is within 2 weeks before the first dose; 2. A history of severe heart disease, such as: heart failure of New York Heart Association (NYHA) class >=2, myocardial infarction within 6 months, uncontrolled/unstable angina pectoris, etc.; 3. Prolonged QT interval (QTc > 450 msec in males or QTc > 470 msec in females), complete left bundle branch block, third-degree atrioventricular block; severe arrhythmia (except for those stabilized for 2 weeks after treatment with antiarrhythmic drugs); 4. Active autoimmune diseases and inflammatory diseases, such as: systemic lupus erythematosus, psoriasis requiring systemic treatment, rheumatoid arthritis, inflammatory bowel disease, Hashimoto's thyroiditis, etc.; exceptions include: type 1 diabetes mellitus, hypothyroidism controllable with replacement therapy only, and skin diseases that do not require systemic treatment (e.g., vitiligo, psoriasis); 5. Diagnosis of other malignant tumors within 5 years before the first dose, except for the following cases: radically treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin, and/or carcinoma in situ with radical resection; 6. Hypertension poorly controlled with two antihypertensive drugs (systolic blood pressure > 150 mmHg or diastolic blood pressure > 100 mmHg); 7. Patients with poorly controlled blood glucose (defined as: a) two fasting blood glucose measurements > 10 mmol/L, or b) glycated hemoglobin level >= 8%), or complicated with diabetic gangrene; 8. A history of interstitial lung disease (ILD) requiring hormone therapy (including pulmonary fibrosis or radiation pneumonitis), current ILD, or grade >= 2 radiation pneumonitis; 9. Severe respiratory impairment caused by concurrent lung diseases, including but not limited to the following conditions: a) Any underlying lung disease (e.g., pulmonary embolism, severe or critical asthma, severe or very severe chronic obstructive pulmonary disease within 3 months before randomization); b) Restrictive lung disease; 10. Patients with massive serous cavity effusion, symptomatic serous cavity effusion, or poorly controlled serous cavity effusion (poorly controlled is defined as: requiring puncture and drainage at least twice within 1 month); 11. Imaging findings indicating that the tumor has invaded or surrounded large blood vessels in the chest, neck, or pharynx, except when the investigator determines that it does not affect the patient’s enrollment and medication; 12. Thrombotic events such as unstable deep vein thrombosis, arterial thrombosis, or pulmonary embolism requiring therapeutic intervention within 6 months before screening; exceptions include infusion-related thrombosis; 13. Patients with central nervous system (CNS) metastasis and/or carcinomatous meningitis (meningeal metastasis). Patients with stable brain metastases who have received treatment for brain metastasis (radiotherapy or surgery; and have completed radiotherapy/surgery
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Dose-Limiting Toxicity, Maximum Tolerated Dose;Recommended Phase II Clinical Research Dose (RP2D);Objective response rate (ORR;Disease Control Rate (DCR;Duration of remission (DOR; | — |
Secondary
| Measure | Time frame |
|---|---|
| Types, frequencies, and severities of treatment-emergent adverse events (TEAEs);Pharmacokinetic (PK) parameters: Cmax, Tmax, T1/2, AUC0-t, CL, Ctrough, etc.;Immunogenicity: Incidence of anti-BL-B01D1 antibodies; | — |
Countries
China
Contacts
Public ContactZhou Fei
Shanghai East Hospital
Outcome results
None listed