locally advanced or metastatic NSCLC Harboring EGFR Mutations
Conditions
Interventions
Dose escalation: SYS6010+ Osimertinib:SYS6010+ Osimertinib,fix the dose of Osimertinib 80mg/d, dose escalation of SYS6010
Dose selection: SYS6010+ Osimertinib:SYS6010 higher dose group was selected for combined administration, Osimertinib 80mg/d
Dose selection: SYS6010+ Osimertinib:SYS6010 lower dose group was selected for combined administration, Osimertinib 80mg/d
Dose selection: Osimertinib:Osimertinib 80mg/d
Sponsors
Shanghai Chest Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. aged >=18 years and = 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 or erythropoietin (EPO) within 2 weeks prior to the first administration of investigational drugs (1) Absolute neutrophil count (ANC) >=1.5×10^9/L; (2) Platelet count (PLT) >=100×10^9/L; (3) Hemoglobin (HGB) >=90 g/L; Renal Function: (4) Serum creatinine (Cr) =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 7 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 meningeal metastasis, brain stem metastasis, spinal cord metastasis and/or compression, or active CNS metastasis; 2. With history of other malignant tumors within 3 years before the first administration of the investigational drugs, 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 or Osimertinib, or to humanized monoclonal antibody products. 4. 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). 5. 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, or 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 inducers or inhibitors, OATP1B1 or OATP1B3 inhibitors within 2 weeks prior to the first dose; (4) Investigational drugs or live attenuated vaccine within 4 weeks prior to the first dose. 6. The patients with a history of severe cardiovascular disease within 6 months before the first dose of the investigational drugs, 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 or 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 7. 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. 8. 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. Active infection requiring systemic antibiotics within 2 weeks prior to the first use of the investigational drugs. 9. Currently has a skin condition that requires oral or intravenous administration. 10. History of the following ophthalmic conditions: severe dry eye syndrome, severe keratitis, severe conjunctivitis, and other conditions which may lead to an increased risk of corneal epithelial injury judged by the investigator. 11. 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 hyp
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Phase Ib: Occurrence and frequency of Adverse Event (AE);Phase Ib: Safety endpoint: Occurrence and frequency of Serious Adverse Event (SAE);Phase Ib: Safety endpoint: Dose-limiting Toxicity (DLT);Phase Ib: The maximum tolerated dose (MTD) (if available);Phase Ib: Recommended phase 3 dose (RP3D);Phase Ib: Objective Response Rate (ORR);plasma concentration and/or PK Parameters of toxin-binding antibodies, total antibodies and free toxin after single and continuous administration of SYS6010;Immunogenicity: the incidence and the titer of anti-SYS6010 antibodies (ADA) and neutralizing antibodies (if applicable), proportion of ADA positive participants, the time and duration of the first ADA positive occurrence of participants;EGFR mutations, amplifications, protein expressions, other tumor-related gene variants; | — |
Secondary
| Measure | Time frame |
|---|---|
| Phase Ib: PFS evaluated by investigators;;Phase Ib: OS;Phase Ib: DoR evaluated by investigators;Phase Ib: DCR evaluated by investigators; | — |
Countries
China
Contacts
Public ContactShun Lu
Shanghai Chest Hospital
Outcome results
None listed