Amgen announced new combination study results from the Phase 1b CodeBreaK 101 study, a comprehensive global master protocol trial evaluating the safety and efficacy of LUMAKRAS™ (sotorasib), the first and only approved KRASG12C inhibitor, in more than 10 different investigational combination regimens for the treatment of patients with KRAS G12C-mutated cancers. Results from two arms of the study — LUMAKRAS with afatinib, a pan-ErbB tyrosine kinase inhibitor, and LUMAKRAS with trametinib, a mitogen-activated protein kinase inhibitor (MEKi) — will be presented at the plenary session titled 'Drugging Difficult Targets' during the AACR-NCI-EORTC 2021 Virtual International Conference on Molecular Targets and Cancer Therapeutics on Saturday, Oct. 9, 2021. The LUMAKRAS and afatinib combination arm enrolled 33 heavily pre-treated patients with KRAS G12C-mutated non-small cell lung cancer (NSCLC), including five patients previously treated with LUMAKRAS monotherapy. Ten patients received 20 mg of afatinib/960 mg of sotorasib (cohort 1; 4 patients with prior LUMAKRAS experience) and 23 patients received 30 mg of afatinib/960 mg of sotorasib (cohort 2; 1 patient with prior LUMAKRAS experience). The objective response rate (ORR) was 20% in cohort 1 and 35% in cohort 2, and the disease control rate was 70% and 74% in the two cohorts, respectively. The most common treatment-related adverse events (TRAEs) for this study were diarrhea, nausea, and vomiting. TRAEs of grade 3 occurred in 30% of patients in both dose groups with diarrhea being the most common. In CodeBreaK 101, the combination of LUMAKRAS and trametinib showed antitumor activity in heavily pre-treated patients with KRAS G12C-mutated solid tumors, including those with prior KRASG12C inhibitor treatment. A total of 41 patients were enrolled in the Phase 1b study with 18 patients with NSCLC, 18 patients with colorectal cancer (CRC) and five patients with other solid tumors. The maximum tolerated dose tested was 2 mg trametinib/960 mg sotorasib administered daily. In patients with CRC who were KRASG12C inhibitor naïve, 9% achieved partial response (1 of 11), and 82% achieved disease control (9 of 11). In patients who were previously treated with a KRASG12C inhibitor, 14% achieved partial response (1 of 7), and 86% achieved disease control (6 of 7). In patients with NSCLC who were KRASG12C inhibitor naïve, 20% achieved partial response (3 of 15) and 87% achieved disease control (13 of 15). In patients who were previously treated with a KRASG12C inhibitor, 67% achieved disease control (2 of 3).