The Efficacy and Safety of IBI351 Plus Cetuximab β in Untreated, Locally Advanced or Metastatic Non-small Cell Lung Cancer With KRAS G12C Mutation: A Single-arm, Prospective, Multicenter Phase II Clinical Study
Design: a Phase II, single-arm, multicenter, prospective, interventional study. Target Population: Subjects with previously untreated, locally advanced or metastatic non-small cell lung cancer (NSCLC) confirmed to harbor the KRAS G12C mutation. Treatment Regimen: All enrolled subjects will receive IBI351 combined with cetuximab β injection. Treatment will continue until disease progression (as assessed by the investigator per RECIST 1.1 criteria) or the occurrence of intolerable toxicity. Primary Endpoint: Objective Response Rate (ORR) as assessed by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Secondary Endpoints: Disease Control Rate (DCR), Time to Response (TTR), Progression-Free Survival (PFS), and Overall Survival (OS) , and safety.
• Voluntarily participate in the study and sign the informed consent form (ICF).
• Male or female subjects aged ≥18 years and ≤75 years at the time of signing the ICF.
• Life expectancy ≥ 3 months.
• Histologically or cytologically confirmed unresectable locally advanced (Stage IIIB/IIIC), metastatic, or recurrent (Stage IV) non-small cell lung cancer (NSCLC), per the International Association for the Study of Lung Cancer (IASLC) and American Joint Committee on Cancer (AJCC) 8th edition TNM staging, and not candidates for curative concurrent chemoradiotherapy.
• Documented KRAS G12C mutation confirmed by a written report from a certified laboratory.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0 or 1.
• No prior systemic anti-tumor therapy for locally advanced or metastatic non-squamous NSCLC. Subjects who received prior adjuvant therapy are eligible provided disease recurrence occurred ≥6 months after the last dose of adjuvant therapy or the last session of radical radiotherapy.
• At least one measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Lesions within a prior radiation field or after local therapy can be considered target lesions if documented progression is evident.
• Adequate organ and bone marrow function, defined as:
⁃ 1）Hematopoietic: Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L, platelet count ≥ 100 × 10⁹/L, hemoglobin ≥ 9 g/dL. No transfusion or treatment with granulocyte colony-stimulating factor (G-CSF), thrombopoietin, or erythropoietin within 14 days prior to hematology tests.
⁃ 2）Hepatic: Total bilirubin (TBIL) \< 1.5 × upper limit of normal (ULN), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \< 2.5 × ULN. For subjects with Gilbert's syndrome, TBIL \< 2 × ULN is acceptable. For subjects with liver metastases, AST and ALT \< 5.0 × ULN is required. If direct bilirubin (DBIL) suggests extrahepatic obstruction, TBIL \< 3.0 × ULN is permitted.
⁃ 3）Renal: Serum creatinine (Cr) ≤ 1.5 × ULN OR calculated creatinine clearance (CrCl) ≥ 60 mL/min (using the Cockcroft-Gault formula) if Cr \> 1.5 × ULN.
⁃ 4）Coagulation: Prothrombin time (PT) / activated partial thromboplastin time (APTT) \< 1.5 × ULN and international normalized ratio (INR) \< 1.5 or within the therapeutic range for subjects on anticoagulation therapy.
⁃ 5）Magnesium: Serum magnesium within normal limits. 10. Toxicities from prior anti-tumor therapy must have resolved to baseline or ≤ Grade 1 (except for residual alopecia; neurotoxicity ≤ Grade 2 is acceptable). Subjects with prior immune-related endocrine adverse events (irAEs) from immunotherapy (e.g., hypothyroidism) that are asymptomatic and stably controlled with ongoing hormone replacement or physiologic doses of corticosteroids may be enrolled if the investigator judges that this will not affect study drug administration or safety assessment.
⁃ 11\. Female subjects of childbearing potential or male subjects with partners of childbearing potential must use effective contraception from signing the ICF until 6 months after the last dose of study drug. Female subjects of childbearing potential must have a negative serum pregnancy test within 7 days (inclusive) prior to the first dose. If a urine pregnancy test result is inconclusive, a serum pregnancy test is required.