SKB264 Plus Goleirex in Advanced KRAS G12C-Mutant NSCLC: A Phase II Study

This is a multicenter, single-arm, phase II (Simon two-stage) prospective interventional clinical study. The primary objective is to evaluate the efficacy and safety of lucankizumab (SKB264) in combination with golelixir (a KRAS G12C inhibitor) as first-line treatment in patients with KRAS G12C-mutated locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC). Specifically, the primary endpoint is the objective response rate (ORR) assessed by investigators per RECIST 1.1 to verify the core antitumor activity of the combination regimen. Secondary objectives include comprehensive evaluation of overall efficacy via disease control rate (DCR), duration of response (DoR), time to response (TTR), progression-free survival (PFS), and overall survival (OS). Safety will be monitored in accordance with NCI CTCAE 5.0, including the incidence and severity of adverse events (AEs) and serious adverse events (SAEs), to characterize the safety profile of the combination and the feasibility of dose modifications. This study aims to provide scientific evidence for the use of this combination regimen as first-line therapy for KRAS G12C-mutated advanced NSCLC and to explore a more optimal treatment option for this patient population.

Inclusion Criteria: * 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. * Expected survival time of ≥3 months. * Histologically or cytologically confirmed non-squamous non-small cell lung cancer (NSCLC) with unresectable locally advanced stage (Stage ⅢB/ⅢC), metastatic or recurrent stage (Stage Ⅳ) that is not eligible for radical concurrent chemoradiotherapy, in accordance with the 8th edition of the TNM --Staging System for Lung Cancer by the International Association for the Study of Lung Cancer (IASLC) and the American Joint Committee on Cancer (AJCC). Confirmed KRAS G12C mutation-positive by a qualified laboratory (CAP/CLIA or nationally accredited) using next-generation sequencing (NGS) or an equivalent method; positivity in either tissue samples or plasma circulating tumor DNA (ctDNA) is acceptable. If plasma testing is negative and tissue testing is feasible, supplementary tissue testing is recommended. * Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0 to 1. * Definition for first-line systemic therapy of advanced disease: No prior systemic anti-tumor therapy for metastatic/advanced disease. For subjects who previously received radical post-surgical therapy, chemoradiotherapy or immunotherapy alone, enrollment is permitted only if the interval from the last dose to disease recurrence is ≥6 months. * Presence of at least one measurable lesion in accordance with the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1; measurable lesions within a prior radiotherapy field or after local treatment may be selected as target lesions if disease progression is documented. * Sufficient organ and bone marrow function, including the following: Adequate hematopoietic function: Absolute neutrophil count (ANC) ≥1.5×10⁹/L, platelet count ≥100×10⁹/L, hemoglobin ≥9 g/dL. No blood transfusion or treatment with granulocyte colony-stimulating factor (G-CSF), thrombopoietin (TPO), erythropoietin (EPO) or other similar agents is allowed within 14 days prior to blood routine testing. * Adequate liver function: Total bilirubin (TBIL) \