KRYSTAL-12
Confirmed that the KRAS pill adagrasib beats chemotherapy after first-line treatment, though the gain is modest.
453 patients. PFS 5.5 vs 3.8 months (HR 0.58); ORR 32% vs 9%; intracranial ORR 24% vs 11%. OS not yet significant. Supports full approval and the second-line role of G12C inhibitors while first-line combinations mature.
Setting
Previously treated KRAS G12C NSCLC: adagrasib vs docetaxel
Phase
Phase 3
Sponsor
BMS (Mirati)
Registry
Headline result
PFS HR 0.58.
Reported
2024
Enrolled
453
Replication
Consistent with CodeBreaK 200 (sotorasib vs docetaxel, PFS HR 0.66); neither trial showed an OS benefit.
In plain words
What these results mean for people, not percentages
Progression-free survival (BICR)primarysurrogate endpoint
- Median 5.5 vs 3.8 months with Adagrasib compared with Docetaxel; about 1.7 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 42 percent lower chance of the event at any given time (hazard ratio 0.58, likely range 0.45 to 0.76).
- 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.
- These results apply to the people the trial enrolled: Previously treated KRAS G12C NSCLC: adagrasib 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.
453 participants enrolled.
Progression-free survival (BICR)primary
HR 0.58 (0.45–0.76) · p <0.0001
Adagrasib
5.5 mo
Docetaxel
3.8 mo
| Endpoint | Arm | n | Value | HR (95% CI) | p | Source |
|---|---|---|---|---|---|---|
| Progression-free survival (BICR)primary | Adagrasib | 301 | 5.5 months | 0.58 (0.45–0.76) | <0.0001 | link |
| Docetaxel | 152 | 3.8 months |
Replication
Consistent with CodeBreaK 200 (sotorasib vs docetaxel, PFS HR 0.66); neither trial showed an OS benefit.