advanced esophageal cancer
Conditions
Interventions
SYS6010+ Enlonstobart:SYS6010+ Enlonstobart
SYS6010+ Enlonstobart+Simmitinib:SYS6010+ Enlonstobart+Simmitinib
Sponsors
The First Affiliated Hospital of Henan University of Science and Technology
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. aged =18 years, = 75 years, regardless of gender; 2. Histological diagnosis of recurrent or metastatic advanced esophageal cancer; 3. Advanced esophageal cancer that has failed previous standard treatment or is intolerant to standard treatment, or refuses standard treatment; 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 of 0-1; 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; 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 sperms. 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 meningeal metastasis, brain stem metastasis, spinal cord metastasis and/or compression, or active CNS metastasis; 2. With a 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 Enlonstobart or Simmitinib, or to humanized monoclonal antibody products. 4. The patients with a history of treatment with topoisomerase I inhibitor based ADC. 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 > 470 ms by Fridericia method (Fridericia formula: QTcF = QT/RR^0.33, RR = 60/heart rate);(2)With a history of myocardial infarction, unstable angina pectoris, aortic dissection, 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.(4)Stroke or other grade 3 or higher cardiovascular and cerebrovascular events 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. Currently has a skin condition that requires oral or intravenous administration. 11. History of the following ophthalmic conditions: severe dry eye syndrome, severe keratitis, severe conjunctivitis, and other conditions judged by the investigator which may lead to an increased risk of corneal epithelial injury. 12. Have an active autoimmune disease or a history of autoimmune disease (e.g Previous ulcerative colitis or Crohn's disease, etc) except for patients with well-controlled type I diabetes, well-controlled hypothyroidism w
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);; | — |
Secondary
| Measure | Time frame |
|---|---|
| plasma concentration and/or PK Parameters (CmaxTmaxt1/2MRTVdCLAUC0-tAUC0-8Rac, etc) of toxin-binding antibodies, total antibodies and free toxin (JS-1) after single and continuous administration of SYS6010; plasma concentration of Enlonstobart; plasma concentration of Simmitinib. Immunogenicity: Incidence and titers of anti-drug antibodies (ADA), incidence of neutralizing antibodies (if applicable), proportion of ADA-positive participants, time and duration of participants' first ADA pos; | — |
Countries
The people's Republic of China
Contacts
Public ContactShegan Gao
The First Affiliated Hospital of Henan University of Science & Technology
Outcome results
None listed