EGFR and ALK wild type locally advanced or metastatic NSCLC and other advanced solid tumor
Conditions
Interventions
SYS6010+Enlonstobart:SYS6010+Enlonstobart
SYS6010+Enlonstobart+Carboplatin:SYS6010+Enlonstobart+Carboplatin
SYS6010+Enlonstobart+Cisplatin:SYS6010+Enlonstobart+Cisplatin
Sponsors
Shanghai East Hospital
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 advanced NSCLC and other advanced solid tumor: Dose-escalation and PK extension study will include patients who have failed or are intolerant to standard treatment, have no standard treatment or have refused standard of care; Cohort extension stage (except cohort B5) will include patients who have not previously received systemic treatment. Patients who have received adjuvant or neoadjuvant chemotherapy appear recurrence or metastasis more than 6 months from accepting the last dose of therapy drugs will be allowed for inclusion. Cohort extension cohort B5 will include patients with lung squamous cell carcinoma who achieved remission after first-line immunotherapy combined with platinum-containing double-agent chemotherapy. 3. Phase II Part 1, PD-L1 protein expression can be included based on the results of previous 22C3 antibody detection, but enrolled participants need to provide enough tumor tissue samples to send to the central laboratory for retesting of PD-L1 protein expression. If the previous test results cannot be provided, the test results of the central laboratory shall prevail. For patients with non-squamous NSCLC, the confirmation of EGFR and ALK gene wild type is mainly based on the previous detection results of tumor tissues, any previous detection results of tumor tissues or blood samples with mutant type do not meet the inclusion criteria. In the absence of previous detection results, the results of the central laboratory shall prevail. Patients with squamous non-small cell lung cancer who have known EGFR and ALK gene mutations do not meet the inclusion criteria and do not need to be sent to a central laboratory for further testing without prior test results. 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 reception of 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 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; ? Serum creatinine (for platinum-containing treatment cohort) = ULN and creatinine clearance =60 mL/min ? Urea nitrogen (for platinum-containing treatment cohort) =ULN 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,
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, medulla oblongata or spinal cord) 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 no increased pre-existing brain metastasis lesion, and all neurologically related symptoms stabilized or resolved) and who do not require the treatment with glucocorticoids or who receive prednisone at daily dose 480 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, 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 pneumonia/ pneumonitis requiring glucocorticoid therapy, current interstitial pneumonia /pneumonitis, or whose imaging at screening does not exclude interstitial pneumonia/ 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 EGFR targeted therapy needs to be interrupted for =1 month or permanently discontinued due to skin toxicity. Or 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 with hormone replacement therapy, skin
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); Objective Response Rate (ORR); | — |
Secondary
| Measure | Time frame |
|---|---|
| plasma concentration and/or PK Parameters of toxin-binding antibodies, total antibodies and JS-1 after single or continuous administration of SYS6010; Serum concentration of Enlonstobart; Immunogenicity: incidence and titer of anti-SYS6010/ Enlonstobart antibodies (ADA) and neutralizing antibodies (if applicable); proportion of ADA positive participants, the time and duration of the first ADA positive occurrence, etc; PFSDoRDCROS; EGFR protein experssions and amplifications, PD-L1 protein exp; | — |
Countries
China
Contacts
Public ContactCaicun Zhou
Shanghai East Hospital
Outcome results
None listed