CodeBreaK 100 Phase 2 Study Results Demonstrate Sotorasib Efficacy

Lung cancer is one of the leading causes of cancer-related death. In the United States, more than 230,000 cases of lung cancer are diagnosed each year, with more than 135,000 patient fatalities.1 It is the leading cause of death in men and the second largest cause of death in women, across the globe.1 Non–small-cell lung cancer (NSCLC) accounts for the vast majority of lung cancer cases (80%-85%), with adenocarcinoma being the most frequent subtype.2 KRASG12C mutations are found in approximately 13% of patients with lung adenocarcinoma, making the cancer aggressive and difficult to treat.3

Twenty percent of patients with advanced NSCLC who have previously received therapy had a positive outcome, and the median progression-free survival (PFS) is 4 months.4 Sotorasib, a first-in-class drug, exclusively targets the KRASG12C mutation and binds to the mutant protein in an irreversible manner, turning off cell signaling that causes cell division and cancer progression.3

Sotorasib was well-tolerated in the phase 1 CodeBreaK 100 trial, with a 32% response rate in patients with NSCLC who had been extensively pretreated before sotorasib initiation.4

The phase 2, single-arm CodeBreaK 100 trial assessed the safety and effectiveness of sotorasib in 126 patients with locally advanced or metastatic NSCLC who had a KRASG12C mutation, building on the findings of the phase 1 trial. In addition to having a confirmed KRASG12C mutation, trial participants had to have progressing disease after receiving anti–PD-1/PD-L1 and/or platinum-based combination chemotherapy; received targeted therapy if anaplastic lymphoma kinase, epidermal growth factor receptor, or ROS proto-oncogene 1 molecular alterations were found; and have had received 3 previous lines of therapy. Patients with brain metastases were not allowed to participate in the study. The major end point was the confirmed objective response rate. PFS, median duration of response, disease control rate, and safety were secondary end goals.

In January 2021, the key findings of the phase 2 trial were presented at the International Association for the Study of Lung Cancer 2020 World Conference on Lung Cancer Singapore. Participants in the study were given 960 mg of sotorasib orally once daily.4 At least 1 dose of sotorasib was given to each patient. The majority (117) of participants were current or past smokers, with 123 having ≥1 detectable lesions at the start of the study. The average age of the participants in the study was 63.5 years. The objective response rate was 37.4%, with 46 patients receiving a positive response.4 Duration of response had a 6.9-month median follow-up, with 52.2% of responders staying on medication without disease progression.4 PFS was 6.7 months on average, and the disease control rate was 80.5%.4

The treatment with sotorasib was well-tolerated. In 69.8% of patients, treatment-related adverse events (AEs) were documented. Only 9 patients discontinued treatment due to AEs. Grade 3 AEs occurred in 20.6% of patients, with 6.3% reporting an increase in alanine aminotransferase, 5.6% experiencing an increase in aspartate aminotransferase, and 4% having diarrhea.4 During the research, no fatal AEs were reported. Sotorasib therapy was found to be safe, effective, and well-tolerated in patients with extensively pretreated NSCLC with KRASG12C mutation.


  1. Clark SB, Alsubait S. Non Small Cell Lung Cancer. Treasure Island, FL: StatPearls Publishing; 2021. Accessed December 9, 2021.
  2. American Cancer Society. Cancer facts & figures 2021. Accessed December 9, 2021.
  3. Hong DS, Fakih MG, Strickler JH, et al. KRASG12C inhibition with sotorasib in advanced solid tumors. N Engl J Med. 2020;383:1207-1217.
  4. Li BT, Skoulidis F, Falchook G, et al. CodeBreaK 100: registrational phase 2 trial of sotorasib in KRAS p.G12C mutated non-small cell lung cancer. Presented at: IASLC 2020 World Conference on Lung Cancer Singapore; January 30, 2021. Abstract PS01.07.

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