Sotorasib for Lung Cancers with KRAS p.G12C Mutation
- Study type
- Clinical trial
- Study name
- CodeBreaK 100
- Phase
- Phase 2
- Design
- Single-arm phase 2 trial (no control group)
- Sample size
- 126 patients
- Source
- N Engl J Med · 2021
- Trial registration
- NCT03600883
In plain words
Sotorasib is a tablet that specifically targets the KRAS G12C mutation in lung cancer. In this study, the tumour shrank in about a third (37.1%) of patients who had already had standard treatments, and in most of them (80.6%) the disease was kept under control. Most patients had side effects, but serious ones (grade 3 and 4) were seen in about 20% of patients, and no new safety problem was reported.
Key results
Treatment arms and regimens
Sotorasib 960 mg orally once daily until disease progression, unacceptable toxicity or patient withdrawal (126 patients; median duration of treatment 5.5 months; dose reduction in 20.6%).
FDA label notes (Lumakras): 960 mg (three 320 mg, four 240 mg or eight 120 mg tablets) once daily at the same time each day, with or without food, tablets swallowed whole. Dose reduction: 480 mg, then 240 mg; if 240 mg is not tolerated, discontinue. Liver tests every 3 weeks for the first 3 months, then monthly. Avoid proton pump inhibitors and H2 antagonists; if an acid-reducing agent is needed, take sotorasib 4 hours before or 10 hours after a local antacid.
Source of the regimen details: Full text of the paper (PMC9116274) and the FDA label for Lumakras (DailyMed, 2025 version)
Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.
Study population
Patients aged 18 years or older with locally advanced or metastatic NSCLC with a KRAS p.G12C mutation confirmed by the central laboratory (therascreen KRAS RGQ PCR), who had progressed after anti-PD-1/PD-L1 immunotherapy or platinum-based combination chemotherapy (or both); ECOG 0 to 1; measurable disease (RECIST 1.1). Exclusion criteria: active untreated brain metastases, more than 3 previous lines of therapy, systemic therapy within 28 days or radiotherapy within 2 weeks before starting, and a previous direct KRAS G12C inhibitor.
Most patients (81.0%) had previously received both platinum chemotherapy and a PD-1 or PD-L1 inhibitor. Of the 126 patients, 124 had measurable disease and were evaluated for response.
Endpoints
Primary endpoint: objective response (complete or partial response) by independent central review.
Key secondary endpoints: duration of response, disease control (complete response, partial response or stable disease), progression-free survival, overall survival and safety. Exploratory biomarkers were also assessed for association with response to sotorasib.
Safety and side effects
Treatment-related adverse events occurred in 88 of 126 patients (69.8%), including grade 3 events in 25 patients (19.8%) and one grade 4 event in one patient (0.8%; pneumonitis and dyspnoea); no fatal treatment-related adverse events were reported. The most common treatment-related adverse events: diarrhoea 31.7%, nausea 19.0%, ALT increase 15.1%, AST increase 15.1% and fatigue 11.1%.
Treatment-related adverse events led to dose modification (interruption, reduction or both) in 22.2% and discontinuation in 7.1% (most common causes of modification: diarrhoea, AST and ALT increase). Worst grade of adverse events regardless of relationship to the drug: grade 3 in 42.1%, grade 4 in 3.2% and grade 5 in 15.9%.
Clinical significance and place in guidelines
Based on the abstract, sotorasib showed durable antitumour activity and acceptable safety in previously treated patients with KRAS p.G12C-mutated NSCLC and may be a targeted option for this group. This is a single-arm study; drug approval status and its place in treatment guidelines should be checked separately.
Limitations
This was a single-arm phase 2 trial with no control group, so direct comparison with other treatments is not possible. The upper limit of the confidence interval for duration of response and overall survival could not be evaluated (the data were not yet mature). Biomarker assessment was exploratory.
This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.