Resectable Stage II-IIIB non-squamous non-small cell lung cancer with EGFRm
Conditions
Interventions
Trial group:SYS6010 4.5 mg/kg via intravenous infusion every 3 weeks (Q3W), in combination with osimertinib 80 mg orally once daily (QD), with one treatment cycle lasting 3 weeks.
Control group:Osimertinib 80 mg orally once daily (QD), with one treatment cycle lasting 3 weeks.
Sponsors
Shanghai Chest Hospital; Shanghai Pulmonary Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. Able to understand and voluntarily sign the written Informed Consent Form (ICF); 2. Age 18–75 years, either sex; 3. Histologically or cytologically confirmed (with pathology report) non-squamous non-small cell lung cancer (NSCLC), staged as resectable or potentially resectable Stage II–IIIB disease according to the IASLC 8th Edition TNM Staging System (lymph node involvement limited to N2), and eligible for lobectomy, sleeve resection, or bilobectomy at the time of screening; 4. At screening, the participant must be evaluated by a multidisciplinary team (including at least a thoracic surgeon performing lung cancer surgery) and deemed eligible for complete surgical resection of the primary tumor; T4 tumors are eligible only if T4 status is defined solely by tumor size (>=7 cm); any other cause of T4 classification (e.g., invasion or adhesion to diaphragm, mediastinum, heart, great vessels, trachea, recurrent laryngeal nerve, esophagus, vertebrae, or carina) is excluded; 5. Lymph node status must be assessed by whole-body 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) and contrast-enhanced CT. If mediastinal lymph nodes are suspected positive on imaging, histological confirmation is required, preferably via endobronchial ultrasound (EBUS) or endoscopic ultrasound (EUS); mediastinoscopy or thoracoscopy may be used as alternatives for lymph node biopsy; 6. Confirmed by central or local laboratory testing the presence of an EGFR sensitizing mutation (exon 19 deletion or exon 21 L858R mutation; coexistence with other EGFR mutations is permitted); 7. No prior systemic anti-tumor therapy (including chemotherapy, biologic therapy, targeted therapy, or immunotherapy); 8. At least one measurable lesion according to RECIST v1.1 criteria at baseline; 9. ECOG Performance Status (PS) score of 0 or 1; 10. Expected survival time >= 6 months; 11. Major organ and bone marrow function must meet the following criteria within 7 days prior to first dose: (1) Hematological parameters: 1) Absolute neutrophil count (ANC) >= 1.5×10^9/L (without administration of hematopoietic growth factors within 7 days prior to hematological assessment, and no long-acting granulocyte colony-stimulating factor (G-CSF) or pegylated recombinant human G-CSF (PEG-CSF) within 14 days prior); 2) Platelet count >= 100×10^9/L (without platelet transfusion or recombinant human thrombopoietin within 7 days prior to hematological assessment); 3) Hemoglobin >= 100 g/L (without red blood cell transfusion within 14 days prior to hematological assessment); (2) Renal function: serum creatinine = 50 mL/min (calculated using the Cockcroft-Gault formula; see Appendix 13.8); (3) Hepatic function: 1) Total bilirubin <= 1.5×ULN (<= 3×ULN for Gilbert’s syndrome); 2) Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <= 2.5×ULN; (4) Coagulation function: 1) International normalized ratio (INR) <= 1.5×ULN; 2) Activated partial thromboplastin time (APTT) <= 1.5×ULN; 12. Women of childbearing potential must use highly effective contraception. A negative pregnancy test must be confirmed in women of childbearing potential within 7 days prior to randomization. All participants of childbearing potential—both male and female—must agree to use highly effective contraceptive methods throughout the trial and for 7 months
Exclusion criteria
Exclusion criteria: 1. Diagnosis of Stage I, N3 Stage IIIB, Stage IIIC, Stage IVA, or Stage IVB non-small cell lung cancer (NSCLC); 2. Dual or multiple primary tumors (if dual primary lung cancers, refer to exclusion criterion 8), or mixed histological subtypes including small cell lung cancer and other types of NSCLC; 3. NSCLC diagnosed as T4 due to invasion of major vessels, carina, trachea, esophagus, heart, and/or vertebrae; and/or any large N2-stage NSCLC; 4. Eligible only for segmentectomy or wedge resection; 5. Received traditional Chinese medicine formulations indicated for lung cancer treatment within 1 week prior to randomization; 6. Underwent major surgery or suffered severe traumatic injury within 4 weeks prior to first study treatment, or is anticipated to undergo major surgery during the study period. Minor procedures such as vascular access placement or biopsy are permitted; 7. Simultaneously enrolled in another clinical trial, unless the other trial is an observational (non-interventional) study or the participant is in the follow-up phase of an interventional trial; 8. History of other primary malignancies (including any known or suspected concurrent primary lung cancer), except for the following: (1) Malignancies treated with curative intent and with no evidence of active disease for at least 2 years prior to first study drug administration, and with low risk of recurrence; (2) Adequately treated skin cancer (excluding malignant melanoma) with no evidence of disease progression; (3) Adequately treated carcinoma in situ with no evidence of disease progression; (4) Concurrent IA-stage primary lung cancer measuring 100 IU/mL), at least 6 weeks of antiviral therapy must be initiated prior to study treatment, with HBV DNA < 100 IU/mL and transaminases < 1 ULN; (3) For prior or chronic HBV infection, eligibility requires meeting one of the following: 1) HBsAg negative and anti-HBc IgG or total anti-HBc antibody positive; patients must be evaluated by a local hepatology specialist and managed according to local guidelines; 2) Or HBsAg positive, with transaminases persistently norma
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To evaluate the difference in major pathological response (MPR) rate, based on blinded independent pathological review (BIPR), in participants with non-squamous non-small cell lung cancer with EGFR m receiving SYS6010 combined with osimertinib versus osimertinib monotherapy as neoadjuvant therapy; | — |
Secondary
| Measure | Time frame |
|---|---|
| To evaluate the difference in pathological complete response (pCR) rate, based on BIPR, in participants with non-squamous non-small cell lung cancer with EGFR-sensitizing mutations receiving SYS6010 combined with osimertinib versus osimertinib monotherapy as neoadjuvant therapy;To evaluate the difference in TNM downstaging in participants with non-squamous non-small cell lung cancer with EGFR-sensitizing mutations receiving SYS6010 combined with osimertinib versus osimertinib monotherapy as neoadjuvant therapy;To evaluate the differences in objective response rate (ORR), event-free survival (EFS), and disease-free survival (DFS), based on investigator assessment, in participants with non-squamous non-small cell lung cancer with EGFR-sensitizing mutations receiving SYS6010 combined with osimertinib versus osimertinib monotherapy as perioperative therapy;To evaluate the difference in overall survival (OS) in participants with non-squamous non-small cell lung cancer with EGFR-sensitizing mutations receiving SYS6010 combined with osimertinib versus osimertinib monotherapy as perioperative therapy;To evaluate the differences in safety and tolerability based on treatment-emergent adverse events (TEAEs) in participants receiving SYS6010 combined with osimertinib versus osimertinib monotherapy;To evaluate the pharmacokinetic (PK) characteristics of SYS6010;To evaluate the immunogenicity of SYS6010 To assess the correlation between clinical efficacy and the clearance of circulating tumor DNA (ctDNA) and EGFR-related gene variations at different time points (screening, pre-surgery, 12 weeks [±2 weeks], 24 weeks [±2 weeks] post-surgery, and every 24 weeks thereafter for up to 3 years post-surgery); | — |
Countries
China
Contacts
Public ContactLi Ziming; Zhang Peng
Shanghai Chest Hospital; Shanghai Pulmonary Hospital
Outcome results
None listed