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 SKB264 in combination with Glecirasib (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.
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).
Prior treatment with a KRAS G12C inhibitor or TROP2-ADC; any prior systemic anti-tumor therapy (chemotherapy, immunotherapy, targeted therapy, etc.) for advanced non-small cell lung cancer (NSCLC).
Positive for other clinically approved first-line targetable oncogenic drivers: classic sensitizing EGFR mutations (19del/L858R), ALK/ROS1/RET/NTRK fusions, BRAF V600E mutation, MET exon 14 skipping mutation, and other mutations for which guideline-recommended approved first-line targeted therapies are available (to avoid conflict with current standard of care); concurrent mutations such as KRAS combined with STK11/KEAP1 are not exclusion criteria.
Histologically or cytologically confirmed mixed NSCLC with small cell carcinoma components or predominantly squamous cell carcinoma components.
Single group
SKB264
Drug4 mg/kg intravenously every 2 weeks
Goleirex
Drug600 mg orally once daily
Objective Response Rate as Assessed by RECIST v1.1
Objective response rate (ORR) refers to the proportion of patients whose tumors have shrunk to a certain extent and maintained that state for a certain period of time, including cases of complete response (CR) and partial response (PR) as assessed by RECIST v1.1.
Progression-free Survival as Assessed by RECIST v1.1
Progression-free survival (PFS) refers to the period from the start of combined treatment until any objectively recorded tumor progression occurs or until the patient's death (for patients lost to follow-up, it is the last follow-up time; for patients still alive at the end of the study, it is the date of the follow-up termination) as assessed by RECIST v1.1.
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Second Affiliated Hospital, School of Medicine, Zhejiang University
Lead sponsor
Ruijin Hospital
Collaborator
The First Affiliated Hospital of University of Science and Technology of China
Collaborator
Affiliated Hospital of Jiaxing University
Collaborator
Huzhou Central Hospital
Collaborator
Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University
Collaborator
Ningbo Medical Center Lihuili Hospital
Collaborator
