背景：在注册阶段 2 CodeBreaK 100 试验中，sotorasib 在经预处理的 KRAS p.G12C 突变非小细胞肺癌（NSCLC）的客观应答率为 37.1% （95% Cl： 28.6， 46.2）和中位无进展生存（PFS）为 6.8 个月（95%Cl：5.1，8.2）。在携带 STK11 共突变的患者中观察到肿瘤反应，这是临床结果不佳、护理标准低下的驱动因素。在这里，我们按关键基线特征和生物标记报告一组扩展亚组的疗效。

Background: In the registrational phase 2 CodeBreaK 100 trial, sotorasib demonstrated an objective response rate (ORR) of 37.1% (95% Cl: 28.6, 46.2) and a median progression-free survival (PFS) of 6.8 months (95% Cl: 5.1, 8.2) in patients with pretreated KRAS p.G12C mutated non-small cell lung cancer (NSCLC). Tumor response was observed in patients bearing co-mutations in STK11, a driver of poor clinical outcomes with standard of care. Here, we report efficacy across an extended set of patient subgroups by key baseline characteristics and biomarkers.

方法：晚期 NSCLC 携带 KRAS p.G12C 并接受先前标准疗法的符合标准的患者予以每日口服 Sotorasib 960 mg。主要终点由中心重新审核评估 ORR。关键的次要端点包括 PFS、 OS 和安全性。KRAS p.G12C 突变等位基因频率（MAF）和肿瘤突变负担（TMB）通过分析组织样本进行二代测序（NGS）。单个基因的突变状态由组织和/或血浆样本的 NGS 确定。在可获得相应结果的患者亚组中分析了反应与 KRAS p.G12C MAF，TMB 或共突变之间的相关性。MAF 与反应之间的关联为值比 （95% CI），来自依赖变量的对数回归，该对数的自变量是比值比，而 MAF 的自变量以 10%为单位。

Methods: Sotorasib was given orally at 960 mg once daily to eligible patients who had advanced NSCLC harboring KRAS p.G12C and received prior standard therapies. Primary endpoint was ORR assessed by central review. Key secondary endpoints included PFS, overall survival, and safety. KRAS p.G12C mutant allele frequency (MAF) and tumor mutational burden (TMB) were analyzed by next-generation sequencing (NGS) using tissue samples. Mutational status of individual genes was determined by NGS using tissue and/or plasma samples. Correlations between response and KRAS p.G12C MAF, TMB, or co-mutations were analyzed in subsets of patients who had available respective results. Association between MAF and response was reported by odds ratio (95% CI), from a logistic regression with dependent variable of log odds of being a responder and an independent variable of MAF in a unit of 10%.

结果：表中介绍了亚组的 ORR。在研究人群中，应答率是不依赖 KRAS p.G12C MAF（比值比 [95% CI]： 1.11 [0.88， 1.39]）。OS 仍然不成熟。

Results: ORR across subgroups is presented in the Table. Response was independent of KRAS p.G12C MAF in the study population (odds ratio [95% CI]: 1.11 [0.88, 1.39]). OS remained immature.

结论：在对 2 期 CodeBreaK 100 临床试验的探索性分析中，在患者亚组中观察到了sotorasib 的临床获益。OS 和最新的探索性分析将被呈现。

Conclusions: In the exploratory analyses of the phase 2 CodeBreaK 100 trial, the clinical benefit of sotorasib was observed across patient subgroups. Overall survival and updated exploratory analyses will be presented.