Amgen Announces Successful Phase II Trial of Sotorasib in KRAS G12C-Mutated Non-Small Cell Lung Cancer
Amgen
Developer of Treatment Drugs for Serious Diseases
IASLC
The IASLC is the only global association dedicated to researching and eradicating lung cancer and other thoracic malignancies. Since its inception, the association has grown to include nearly 6,500 members, comprising experts in lung and thoracic cancers from diverse disciplines and over 100 countries. The IASLC works to alleviate the burden of lung cancer on patients, families, and communities by organizing global conferences, funding cutting-edge research, and raising awareness about thoracic cancers among healthcare professionals and the public. Each year, the IASLC hosts the World Conference on Lung Cancer (WCLC), the world’s largest conference dedicated exclusively to thoracic cancers.
Compiled by Fan Dongdong
Recently, Amgen announced that the Phase II CodeBreaK 100 lung cancer trial of Sotorasib (AMG 510) was successful. Amgen plans to release more detailed trial data at the Presidential Symposium of the International Association for the Study of Lung Cancer (IASLC) 2020 World Conference on Lung Cancer (WCLC).
This drug is a first-in-class, reversible, and highly selective small-molecule inhibitor targeting KRAS G12C. The CodeBreaK 100 study primarily enrolled 126 patients with advanced non-small cell lung cancer (NSCLC) harboring KRAS G12C mutations. In the CodeBreaK 100 trial, the sotorasib group demonstrated an objective response rate (ORR) of 37.1%, a disease control rate (DCR) of 80.6%, and a median duration of response of 10 months. Sotorasib was also the first KRAS G12C inhibitor to demonstrate progression-free survival, with a median duration of 6.8 months.
KRAS G12C mutations occur in approximately 13% of NSCLC cases. Sotorasib is a small-molecule inhibitor that specifically and irreversibly binds to the mutant KRAS G12C protein, preventing it from adopting an active conformation. The KRAS protein plays a critical role in normal cellular signaling pathways that regulate cell growth, proliferation, and differentiation. Certain KRAS mutations lead to constitutive protein activation, resulting in abnormal tumor cell growth. The previously completed Phase I CodeBreak 100 trial initially demonstrated the efficacy of sotorasib in patients with KRAS G12C-mutated NSCLC who had progressed after multiple prior lines of therapy.
In this trial, 80% of patients achieved disease control. Among all patients who demonstrated a therapeutic response, 3 achieved complete response and 43 achieved partial response, with a median best tumor reduction of 60% among all responders. Most treatment-related adverse events (TRAEs) were mild to moderate (Grade 1 or 2), and no treatment-related deaths occurred. Twenty-five patients reported Grade 3 TRAEs, and one patient reported a Grade 4 TRAE. The most common TRAEs were diarrhea, nausea, increased alanine aminotransferase, and increased aspartate aminotransferase. TRAEs led to treatment discontinuation in only 7.1% of patients.
Reference Source: Amgen Racks Up Success in Phase II Lung Cancer Trial
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