Sotorasib Meets PFS End Point in Previously Treated, KRAS G12C–Mutated NSCLC


Sotorasib demonstrated superiority and a statistically significant benefit in progression-free survival vs standard-of-care docetaxel in previously treated patients with KRAS G12C–mutated non–small cell lung cancer.

David M. Reese, MD

David M. Reese, MD

Sotorasib (Lumakras) demonstrated superiority and a statistically significant benefit in progression-free survival (PFS) vs standard-of-care docetaxel in previously treated patients with KRAS G12C–mutated non–small cell lung cancer (NSCLC), meeting the primary end point of the phase 3 CodeBreaK 200 trial (NCT04303780).1

Full data from the trial will be presented at an upcoming medical conference.

“Further analyses of the data are ongoing, and we look forward to sharing detailed data at an upcoming medical meeting,” David M. Reese, MD, executive vice president of Research and Development at Amgen, stated in a press release. “We are grateful to all of the investigators and patients who participated in this first randomized, controlled clinical trial of a KRAS G12C inhibitor.”

In May 2021, the FDA approved sotorasib as the first treatment for adult patients with NSCLC whose tumors harbor KRAS G12C mutations and who have received at least 1 prior systemic therapy, based on results from the phase 2 CodeBreaK 100 trial (NCT03600883). In those findings, the KRAS G12C inhibitor elicited an objective response rate (ORR) of 36% (95% CI, 28%-45%) in patients with KRAS G12C–mutated NSCLC who progressed following treatment with immunotherapy and/or chemotherapy.2

The international CodeBreaK 200 trial evaluated sotorasib vs standard-of-care docetaxel in 345 patients who were at least 18 years old with locally advanced and unresectable or metastatic KRAS G12C–mutated NSCLC and received prior treatment with at least platinum-based doublet chemotherapy and a checkpoint inhibitor. Patients were also required to have an ECOG performance status of 0 or 1.3

Key exclusion criteria included active brain metastases, myocardial infarction within 6 months of the first day of study treatment, or gastrointestinal tract disease causing the inability to take oral medication.

Once enrolled, patients were randomly assigned to oral sotorasib once daily or docetaxel. Along with the primary end point of PFS, secondary end points included overall survival, ORR, duration of response, time to response, disease control rate, patient-reported outcomes, quality of life, and safety.

Regarding the safety of sotorasib, data from CodeBreak 100 showed that any-grade hepatotoxicity occurred in 1.7% of patients, including grade 3 hepatotoxicity in 1.4% of patients. Five percent of patients received corticosteroids for the treatment of hepatotoxicity, in addition to dose interruptions and reductions. Additionally, 18% of patients who received sotorasib had increased alanine aminotransferase and increased aspartate aminotransferase, including 6% at grade 3 and 0.6% at grade 4.

Interstitial lung disease (ILD)/pneumonitis was reported in 0.8% of patients, and all cases were Grade 3 or 4 at onset. One patient died due to ILD/pneumonitis. Sotorasib was discontinued due to ILD/pneumonitis in 0.6% of patients.

The most common adverse effects of any grade that occurred in at least 20% of patients included diarrhea, musculoskeletal pain, nausea, fatigue, hepatotoxicity and cough.

Sotorasib is also under investigation in other clinical trials, including the phase 1/2 CodeBreak 101 trial (NCT04185883), which is evaluating the KRAS G12C inhibitor alone and in combination with various agents in patients with solid tumors harboring KRAS G12C mutations.

The phase 2 CodeBreak 201 trial (NCT04933695) is also investigating 2 different doses of oral sotorasib as a first-line treatment for patients with stage IV, KRAS G12C–mutated NSCLC.


  1. Amgen announces topline data from Lumakras® (sotorasib) phase 3 trial in non-small cell lung cancer. News release. Amgen. August 30, 2022. Accessed August 31, 2022.
  2. FDA approves first targeted therapy for lung cancer mutation previously considered resistant to drug therapy. News release. FDA. May 28, 2021. Accessed August 31, 2022.
  3. Study to compare AMG 510 "proposed INN sotorasib" with docetaxel in non­–small cell lung cancer (NSCLC) (CodeBreak 200). Updated August 3, 2022. Accessed August 31, 2022.
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