CodeBreaK 200
The first randomised trial of a KRAS drug: better than chemotherapy on progression, not on survival.
345 patients. PFS 5.6 vs 4.5 months (HR 0.66); ORR 28% vs 13%; OS HR 1.01 (confounded by crossover and dropout). FDA ODAC questioned the PFS benefit in 2023; full approval was not granted on this trial alone.
Setting
Previously treated KRAS G12C NSCLC: sotorasib vs docetaxel
Phase
Phase 3
Sponsor
Amgen
Registry
Headline result
PFS HR 0.66; OS HR 1.01.
Reported
2022
Enrolled
345
Replication
Consistent with KRYSTAL-12 (adagrasib) on PFS; the FDA declined full approval at the 960 mg dose pending further data.
In plain words
What these results mean for people, not percentages
Progression-free survival (BICR)primarysurrogate endpoint
- Median 5.6 vs 4.5 months with Sotorasib compared with Docetaxel; about 1.1 months longer for half the group.
- A median is a midpoint: half the people did better than this and half did worse, so it is not a prediction for any one person.
- Put another way, the treated group had about 34 percent lower chance of the event at any given time (hazard ratio 0.66, likely range 0.51 to 0.86).
- This is a surrogate endpoint: it measures the cancer being controlled or absent on scans and tests, which often, but not always, translates into living longer.
Overall survivalsurvival endpoint
- Median 10.6 vs 11.3 months with Sotorasib compared with Docetaxel; about 0.7 months shorter for half the group.
- A median is a midpoint: half the people did better than this and half did worse, so it is not a prediction for any one person.
- Put another way, the treated group had about 1 percent higher chance of the event at any given time (hazard ratio 1.01).
- Overall survival counts deaths from any cause, so it is the most direct measure of whether a treatment helps people live longer.
- Not significant; crossover permitted.
Be careful
- These results apply to the people the trial enrolled: Previously treated KRAS G12C NSCLC: sotorasib vs docetaxel. People in a different situation may not see the same effect.
- The trial selected people by a biomarker (KRAS); the result should not be assumed for people whose cancer does not have it.
Numbers are from the trial as recorded here; see the source links in the table below. This is orientation, not medical advice: ask your team how closely the trial population matches you.
345 participants enrolled.
Progression-free survival (BICR)primary
HR 0.66 (0.51–0.86) · p = 0.0017
Sotorasib
5.6 mo
Docetaxel
4.5 mo
Overall survival
HR 1.01
Sotorasib
10.6 mo
Docetaxel
11.3 mo
Not significant; crossover permitted
| Endpoint | Arm | n | Value | HR (95% CI) | p | Source |
|---|---|---|---|---|---|---|
| Progression-free survival (BICR)primary | Sotorasib | 171 | 5.6 months | 0.66 (0.51–0.86) | 0.0017 | link |
| Docetaxel | 174 | 4.5 months | ||||
| Overall survival | Sotorasib | — | 10.6 months | 1.01 | — | — |
| Docetaxel | — | 11.3 months |
Replication
Consistent with KRYSTAL-12 (adagrasib) on PFS; the FDA declined full approval at the 960 mg dose pending further data.