Amgen announced results from two analyses of the Phase 2 CodeBreaK 100 clinical trial evaluating LUMAKRAS™ (sotorasib), the first and only KRASG12C inhibitor approved in the U.S., in the treatment of previously treated patients with advanced or metastatic KRAS G12C-mutated non-small cell lung cancer (NSCLC). These new analyses, respectively, provide encouraging evidence of durable systemic anticancer activity in patients with previously treated, stable brain metastases with LUMAKRAS, as well as insights into biomarkers of LUMAKRAS response. Together with a poster describing a recently initiated clinical study of the investigational half-life extended (HLE) bispecific T cell engager (BiTE®) molecule acapatamab (formerly AMG 160) in patients with NSCLC, these data are being featured during the virtual 2021 World Conference on Lung Cancer (WCLC21) hosted by the International Association for the Study of Lung Cancer (IASLC). In a post-hoc analysis (WCLC21 Poster 52.03) of 40 patients (23% of 174 trial participants) with KRAS G12C-mutated advanced NSCLC who had stable, previously treated brain metastases at their enrollment in the CodeBreaK 100 trial, LUMAKRAS achieved a 77.5% disease control rate (DCR), a median progression-free survival (PFS) of 5.3 months and a median overall survival (OS) of 8.3 months. This DCR was similar to patients without brain metastases. In patients evaluable by Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) criteria, 14 of 16 patients (88%) maintained intracranial disease control of their stable brain lesions during LUMAKRAS therapy with two achieving complete responses of non-target lesions. The safety profile of LUMAKRAS in the brain metastases group was consistent with previous reports. Amgen is enrolling patients with active brain metastases in an arm of the CodeBreaK 101 study (NCT04185883). An additional exploratory descriptive analysis of CodeBreaK 100 being presented during a Mini Oral Presentation (MA14.03) examined whether the mutation profile of the tumors, in addition to KRASG12C, is correlated with patients' responses or resistance to LUMAKRAS. An analysis of baseline tumor samples from 65 patients revealed no single genetic signature that predicted LUMAKRAS responses and ongoing evaluations will be needed to further identify potential targetable mechanisms of resistance. However, the KEAP1 mutation, a known driver of poor clinical outcomes, was observed in 7 of 22 patients with early progression and PFS of less than 3 months.