Advanced Solid Tumors
Conditions
Interventions
Test group:SYS6010
Sponsors
Shanghai Chest Hospital
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. Age = 18 years, regardless of gender; 2. The patients with advanced solid tumors by histopathological diagnosis assays who have failed or are intolerant to standard treatment and have no standard treatment or have refused standard of care; 3. Presence of activating mutations, moderate to high expression, or amplification; 4. With at least one measurable lesion identified by CT or MRI according to RECIST v1.1; 5. Eastern Cooperative Oncology Group (ECOG) performance status 0-1 point; 6. Expected survival = 3 months; 7. Main organs meet the following criteria within 7 days before treatment: Hematology: no component blood transfusion, human granulocyte colony-stimulating factor (G-CSF), thrombopoietin (TPO), interleukin-11 and erythropoietin (EPO) within 2 weeks prior to the first administration of investigational drug ? Absolute neutrophil count (ANC) =1.5×10^9/L; ? Platelet count (PLT) =100×10^9/L; ? Hemoglobin (HGB) =90 g/L or =5.6 mmol/L; Renal Function: ? Serum creatinine (Cr) =1.5 × ULN and creatinine clearance =50 mL/min,Based on Cockcroft-Gault formula; Liver function: Total Bilirubin (TBIL) =1.5×ULN, =3×ULN for the patients with Gilbert syndrome/liver metastasis; Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) = 2.5 × ULN, = 5 × ULN for the patients with liver metastasis; Coagulation Function: Activated partial thromboplastin time (APTT)= 1.5×ULN International normalized ratio (INR)= 1.5×ULN 8. The patients must agree to use effective contraception from the time of signing the ICF until 6 months after the last dose, during which the female should be non-lactating and the male should avoid donating sperm. Women of childbearing potential (WOCBP) have a negative result of blood pregnancy test within 7 days prior to the first dose of investigational drug. 9. The patient voluntarily participates in this clinical study, understands the study procedures and is able to sign the written ICF.
Exclusion criteria
Exclusion criteria: 1. With active central nervous system (CNS) metastasis and/or meningeal metastasis. Those with supratentorial and/or cerebellar (i.e., no midbrain, pons, or medulla oblongata) metastases who are stabilized after local treatment within at least 2 weeks prior to the first dose of the investigational drug (imaging showing no new brain metastasis or increased pre-existing brain metastasis lesion, and all neurologically related symptoms stabilized or resolved) and who do not require the treatment with glucocorticoids or receive prednisone at daily dose =10 mg or equivalent dose of other glucocorticoids can participate in the study. 2. With history of other malignant tumors within 3 years before the first administration of the investigational drug, except for the following conditions: cured basal cell or squamous cell carcinoma of the skin, superficial bladder cancer, prostate carcinoma in situ and cervical carcinoma in situ. 3. With known hypersensitivity to any component of the SYS6010 product, or to humanized monoclonal antibody products. 4. Previous treatment with ADC drugs of the same target and toxin. 5. According to NCI-CTCAE v 5.0, AEs caused by previous anti-tumor treatment have not recovered to = Grade 1 (except for toxicities without safety risk as judged by the investigator such as Grade 2 alopecia and peripheral neurotoxicity). 6. Those who fail to meet the washout period requirements for the following drugs or treatments should be excluded: (1) Major surgery (excluding needle biopsy) within 4 weeks prior to the first dose; (2) Chemotherapy, radical radiotherapy, targeted therapy, endocrine therapy, and immunotherapy within 4 weeks before the first dose; oral fluorouracil, small-molecule targeted drugs, traditional Chinese medicine with anti-tumor indications, palliative radiotherapy or local therapy within 2 weeks before the first dose; (3) Glucocorticoid (prednisone >10 mg/day or equivalent dose of similar drugs), intravenous antibiotics, antifungal or antiviral drugs, CYP3A4 strong inducer or inhibitor, OATP1B1, OATP1B3 inhibitors within 2 weeks prior to the first dose; (4) Investigational drug or live attenuated vaccine within 4 weeks prior to the first dose. 7. The patients with a history of severe cardiovascular disease within 6 months before the first dose of the investigational drug, including but not limited to: (1)Severe cardiac rhythm or conduction abnormalities, such as ventricular arrhythmia and third-degree atrioventricular block requiring clinical intervention, corrected QT interval > 480 ms by Fridericia method (Fridericia formula: QTcF = QT/RR^0.33, RR = 60/heart rate);(2)With history of myocardial infarction, unstable angina pectoris, angioplasty and coronary artery bypass surgery;(3)Class II and above heart failure by New York Heart Association (NYHA) classification, left ventricular ejection fraction (LVEF) <50% at screening. 8. The patients with a history of interstitial lung disease (ILD)/ pneumonitis requiring glucocorticoid therapy, current ILD/pneumonitis, or whose imaging at screening does not exclude ILD/pneumonitis . 9. Severe infection within 4 weeks prior to the first administration of the investigational drug, including but not limited to bacteremia, severe pneumonia, active tuberculosis infection, etc. requiring hospitalization. 10. Previous interruption of targeted therapy due to dermatotoxicity or current skin diseases requiring oral or intravenous therapy. 11. History of the following oph
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Occurrence and frequency of Adverse Event (AE) ;Serious Adverse Event (SAE);Dose-limiting Toxicity (DLT);The maximum tolerated dose (MTD) (if available);Recommended phase 2 dose (RP2D) in stage I; | — |
Secondary
| Measure | Time frame |
|---|---|
| PK Parameters of toxin-binding antibodies single and continuous administration of SYS6010;PK Parameters of total antibodies single and continuous administration of SYS6010;PK Parameters of free toxinafter single and continuous administration of SYS6010;Objective Response Rate (ORR);Duration of Response (DoR);Disease Control Rate (DCR);Progression-free Survival (PFS) ;Overall Survival (OS); | — |
Countries
China
Contacts
Public ContactShun Lu
Shanghai Chest Hospital
Outcome results
None listed