Solid Tumor
Conditions
Interventions
Treatment Group(phase Ia):BL-B16D1 for Injection
Treatment Group((phase Ib)):BL-B16D1 for Injection
Sponsors
Sun Yat-sen University Cancer Center
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. Sign the informed consent form voluntarily and follow the protocol requirements; 2. Gender is not limited; 3. Age: >=18 years old and =18 years old (phase Ib); 4. Expected survival time >=3 months; 5. locally advanced or metastatic solid tumors confirmed by histopathology and/or cytology that failed standard treatment or could not obtain standard treatment; 6. Consent to provide archival tumor tissue samples or fresh tissue samples from primary or metastatic lesions within 3 years; 7. Must have at least one extracranial measurable lesion that meets the RECIST v1.1 definition; 8. ECOG 0 or 1; 9. The toxicity of previous antineoplastic therapy has returned to =50%; 11. If no blood transfusion has been received within 14 days prior to the first administration, the organ function level must meet the following requirements and meet the following criteria: 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 =50 mL/min (based on Cockcroft and Gault formula). 12. Coagulation function: international normalized ratio <=1.5, and activated partial thromboplastin time <=1.5ULN; 13. Urinary protein <=2+ or =1000mg/24h; 14. For premenopausal women with childbearing potential, a pregnancy test must be performed within 7 days before starting treatment, serum pregnancy must be negative, and the patient must not be lactating; All enrolled patients (male or female) should use adequate contraception throughout the treatment cycle and for 6 months after completion of treatment.
Exclusion criteria
Exclusion criteria: 1. Within 4 weeks prior to the first administration or within 5 half lives (whichever is shorter), chemotherapy, biological therapy, immunotherapy, curative radiotherapy, major surgery (as defined by the researchers), targeted therapy (including small molecule tyrosine kinase inhibitors), and other anti-tumor treatments have been used; Mitomycin and nitrosoureas should be administered within 6 weeks prior to the first dose; Oral fluorouracil drugs such as Tegio, Capecitabine, or palliative radiotherapy should be administered within 2 weeks prior to the first dose; 2. Had received previous ADC drug therapy with MMAE/MMAF as toxin; 3. 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, etc; 4. QT interval prolongation (male QTc>450 milliseconds or female QTc>470 milliseconds), complete left bundle branch block, and third degree atrioventricular block; 5. Active autoimmune diseases and inflammatory diseases, such as systemic lupus erythematosus, psoriasis requiring systemic treatment, rheumatoid arthritis, inflammatory intestinal diseases and Hashimoto's thyroiditis, excluding type I diabetes, hypothyroidism that can be controlled only by alternative treatment, and skin diseases that do not require systemic treatment (such as vitiligo and psoriasis); 6. Patients with other malignancies or a history of other malignancies, with the exception of cured basal cell or squamous cell carcinoma of the skin, carcinoma in situ of the cervix, papillary carcinoma of the thyroid, ductal carcinoma in situ of the breast, or other malignancies that have survived more than 5 years without disease; 7. Unstable thrombotic events such as deep vein thrombosis, arterial thrombosis, and pulmonary embolism requiring therapeutic intervention within 6 months prior to initial administration; Thrombus formation associated with infusion set is excluded; 8. Hypertension poorly controlled by two antihypertensive medications (systolic >150 mmHg or diastolic >100 mmHg); 9. Patients with poor blood glucose control were defined as: a) fasting blood glucose > 10mmol/L twice, or b) hemoglobin A1c levels of 8% or more, or c) accompanied by diabetic gangrene; 10. Present with >= grade 2 radiation pneumonia as defined by RTOG/EORTC; A history of interstitial lung disease (ILD), including pulmonary fibrosis, or a current ILD, or imaging findings during screening suggest a suspected ILD; 11. Clinically severe respiratory impairment due to pulmonary disease, including but not limited to: a. Any underlying lung disease (e.g., pulmonary embolism, severe asthma, severe chronic obstructive pulmonary disease within 3 months prior to the first dose); b. restrictive lung diseases; c. One side of the lung was previously removed. 12. Patients with primary central nervous system (CNS) tumors or CNS metastases that have failed local treatment. Patients with stable clinical symptoms, no steroid hormones or other treatment for CNS metastasis for >=28 days, and stable imaging during the screening period can be enrolled. 13. Patients with a history of allergy to recombinant humanized antibodies or chimeric antibodies of humans and mice or to any excipient ingredient of BL-B16D1; 14. Previous organ transplantation or allogeneic hematopoietic stem cell transplantation (Allo-HSCT); 15. The cumulative dose of doxorubicin was > 5
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Phase Ia: Maximum tolerated dose (MTD) [Time Frame: Up to 21 days after the first dose];Phase Ib: Recommended Phase II Dose (RP2D) [Time Frame: Up to approximately 24 months];Phase Ia: Dose limiting toxicity (DLT) [Time Frame: Up to 21 days after the first dose]; | — |
Secondary
| Measure | Time frame |
|---|---|
| Treatment-Emergent Adverse Event (TEAE) [Time Frame: Up to approximately 24 months];Cmax?Tmax?T1/2?AUC0-t?CL?Ctrough;ADA (anti-drug antibody) [Time Frame: Up to approximately 24 months];Phase Ib: Objective Response Rate (ORR) [Time Frame: Up to approximately 24 months]? Disease Control Rate (DCR) [Time Frame: Up to approximately 24 months]?Duration of Response (DOR) [Time Frame: Up to approximately 24 months]; | — |
Countries
China
Contacts
Public ContactLi Zhang
Sun Yat-sen University Cancer Center
Outcome results
None listed