Topline results from the phase 2 CodeBreaK 100 clinical trial were consistent with phase 1 data, withthe KRAS inhibitor sotorasib having achieved a satisfactory objective response rate when administered as treatment of patients with KRAS G12C–mutant non–small cell lung cancer, who had failed a median of 2 prior lines of anti-cancer therapies, which could include immunotherapy and/or chemotherapy.
Topline results from the phase 2 CodeBreaK 100 clinical trial were consistent with phase 1 data, withthe KRAS inhibitor sotorasib (AMG 510) having achieved a satisfactory objective response rate (ORR) when administered as treatment of patients with KRAS G12C–mutant non–small cell lung cancer (NSCLC), who had failed a median of 2 prior lines of anti-cancer therapies, which could include immunotherapy and/or chemotherapy, according to a press release from Amgen.1
In addition to the ORR, patients in the study were evaluated for duration of response (DOR) and the results appeared promising with more than half of the patients who responded to sotorasib still on treatment and responding at the time of data cutoff. The safety observed in the phase 2 portion of the study was also consistent with phase 1 data. Detailed results from the trial will be presented during the 2020 World Congress on Lung Cancer in January 2021 and results are planned to be shared with the FDA.
The goal of CodeBreaK 100 is to determine the safety and efficacy of sotorasib in this patient population and other solid tumors. The trial is part of a program led by the Amgen Corporation that includes more than 500 patients across 13 tumor types. The aim of the program is to fill an unmet medical need for patients with KRAS G12C mutations.
“Targeting KRAS has been a 40-year quest that has left patients with limited options. These topline data underscore our belief in the potential for sotorasib to become the standard of care for non–small cell lung cancer patients with the KRAS G12C mutation who remain in need of new treatment options," said David M. Reese, MD, executive vice president of research and development at Amgen, in a statement.
In the phase 1 portion of the study, the ORR was 32.2% in 34 heavily pretreated patients with KRAS G12C–mutant NSCLC treated across all dose levels. The disease control rate achieved in these patients was 88.1%. The median DOR was 10.9 months. In addition, 71.2% of patients had tumor shrinkage after 6 weeks of treatment with sotorasib. The median progression-free survival observed with the drug was 6.3 months.2
The initial safety analysis for the NSCLC cohort of the CodeBreaK 100 trial showed no dose-limiting toxicities and no treatment-related adverse events (TRAEs) leading to death. The most common TRAEs observed were diarrhea (25.4%), alanine aminotransferase (ALT) increase (20.3%), aspartate aminotransferase (AST) increase (20.3%), fatigue (10.2%), and nausea (10.2%). There were also 11 cases of grade 3 or higher TRAEs, which were mostly commonly ALT and AST increases, which led to treatment discontinuation in 1 patient.
CodeBreaK 100 has met its target enrollment of 533 participants. Eligible patients are those with a pathologically documented, locally advanced or metastatic malignancy mutated with KRAS G12C. Patients are required to be at least 18 years of age. The study excludes individuals with active brain metastases from non-brain tumors, myocardial infarction within 6 months of the study start date, and gastrointestinal tract disease that interferes with a patient’s ability to take the study drug.
A phase 3 study of sotorasib recently begun recruiting patients to confirm the phase 1/2 trial results in patients with KRAS-mutant NSCLC.
"We now have more than 500 patients who have been enrolled across clinical studies, and we are rapidly moving forward with a broad-based development program, which includes monotherapy studies in non–small cell lung cancer, colorectal cancer, and other solid tumors harboring the KRAS G12C mutation, as well as a suite of combination studies. We look forward to discussing the current results with the US Food and Drug Administration (FDA) and other regulatory agencies, to determine the best path forward for sotorasib as a potential treatment for patients with NSCLC harboring the KRAS G12C mutation,” stated Reese.
1. Amgen Announces positive topline phase 2 results for investigational KRAS G12C inhibitor sotorasib in advanced non-small cell lung cancer. News release. October 5, 2020. Accessed October 6, 2020. https://bit.ly/33ArLr3
2. Hong DS, Fakih MG, Desai J, et al. KRASG12C inhibition with sotorasib in advanced solid tumors.N Engl J Med. 2020; 383:1207-1217. doi: 10.1056/NEJMoa1917239