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CodeBreaK 100: What the Lung Cancer Trial Found
CodeBreaK 100 tested sotorasib, the first drug to hit KRAS G12C, in advanced lung cancer. About one in three tumours shrank in a single-arm study with no comparison group — enough to open a drug class, not to prove superiority.
Original commentary from the Cancer Explained editorial team.
Please note: this page is educational only — it is not medical advice, and it does not speculate about anyone’s health beyond reliable public reporting. For questions about your own health, talk with your healthcare team.
A target that resisted drugs for four decades
KRAS is one of the most common faulty genes in cancer. It was found in the early 1980s. For most of the years since, it had a reputation as untouchable: the protein it makes is smooth and round, with nowhere obvious for a drug to grip.
Sotorasib exploits one particular version of the fault, called G12C, which swaps a single building block and creates a small pocket the drug can lock into. CodeBreaK 100 was the study that showed the idea works in people.
What the trial did, and did not, set up
| Field | Detail |
|---|---|
| Trial | CodeBreaK 100 |
| Identifier | NCT03600883 |
| Phase | Phase 2 |
| Design | Single-arm — no comparison group |
| Cancer type | Advanced non-small-cell lung cancer with a KRAS p.G12C mutation |
| Treatment | Sotorasib 960 mg by mouth, once a day |
| Primary endpoint | Objective response, judged by independent central review |
The trial amount is listed for the record. Sotorasib dosing has since been revisited, and your own team decides what you take.
126 people enrolled. All had advanced non-small-cell lung cancer carrying KRAS p.G12C, and all had already been through standard treatment: 81.0% had had both platinum chemotherapy and a PD-1 or PD-L1 immune drug. 124 had disease that could be measured on scans and were assessed for response.
Everyone got the same drug. There is no control group, which is the single most important thing to know about the result.
How many tumours responded
46 of the 124 assessable patients responded — 37.1% (95% CI 28.6 to 46.2). In 4 people (3.2%) the cancer was no longer visible on scans. In 42 (33.9%) it shrank without disappearing.
Adding those whose disease held steady, 100 people (80.6%, 95% CI 72.6 to 87.2) had their disease controlled. So most people got something. Only about a third got shrinkage.
How long the benefit lasted
Responses lasted a median of 11.1 months (95% CI 6.9 to not evaluable). Median time before the cancer started growing again was 6.8 months (95% CI 5.1 to 8.2). Median overall survival was 12.5 months (95% CI 10.0 to not evaluable).
Read that together and a pattern emerges: real benefit, arriving for a minority, and generally measured in months rather than years.
Side effects
Side effects the investigators linked to the drug occurred in 88 of the 126 people (69.8%). Most were manageable. Grade 3 events — severe ones — occurred in 25 people (19.8%), and one person had a grade 4 event (0.8%).
Responses turned up across subgroups defined by PD-L1 level, tumour mutational burden, and other faults in STK11, KEAP1 or TP53. The trial does not identify a second test that predicts who will respond.
What this study cannot tell you
- Whether sotorasib beats the alternatives. A single-arm trial can show that a drug does something. It cannot show that it does more than another drug would have.
- Whether it helps people live longer. Overall survival has no comparison group here, so 12.5 months is a description, not a gain.
- What to expect if you do not have the G12C fault. Other KRAS mutations were not eligible; the drug is built for this one.
- How durable it is. A median response of about 11 months in 126 people is a small evidence base for a long-term claim.
Questions about KRAS testing
- Has my tumour been tested for KRAS, and which mutation was found?
- If this is a single-arm result, what would we compare it against for me?
- What would tell us early that it is not working?
Sources
This article was written from the sources below, which were checked on the source-check date shown above.
How this article was prepared
Prepared by Cancer Explained's AI-assisted editorial system and checked against the sources listed below. This article has not been reviewed by a healthcare professional unless a named reviewer is specifically shown.
Cancer Explained is published by the National Cancer Information Foundation as a nonprofit-oriented public-interest education project. It is not a diagnostic service, does not recommend treatments, and is not for emergencies.
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Prevention, possible warning signs, screening, and diagnosis
This story relates to Lung cancer. The information below is general: it does not reveal anything else about a public person’s health, and not every point applies to every cancer. Personal advice depends on age, symptoms, family history, exposures, and medical history.
Prevention and risk reduction
Not every cancer can be prevented. Avoiding tobacco, protecting skin from ultraviolet radiation, limiting alcohol, staying active, and receiving recommended HPV or hepatitis B vaccination can lower the risk of certain cancers. A risk factor is not a prediction or a cause in one individual.
Symptoms and possible early signs
Possible signs vary and are often caused by conditions other than cancer. Changes worth discussing include a new lump, unexplained bleeding or weight loss, a persistent cough, lasting bowel or bladder changes, a changing skin spot, or symptoms that persist or worsen. Some early cancers cause no symptoms.
Screening and early detection
Screening looks for certain cancers before symptoms begin. Recommended tests exist only for some cancers and depend on age and risk. Screening can have benefits and harms; it is not the same as evaluating a new symptom, and there is no single routine scan or blood test that reliably screens for every cancer.
How cancer is diagnosed
Diagnosis may involve a history and exam, imaging, laboratory tests, and often a biopsy. Pathology can identify the cancer type and may test biomarkers that guide treatment. Symptoms, screening results, tumor markers, or online stories alone cannot confirm cancer.
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