CodeBreaK 300
CodeBreaK 300 showed that a KRAS drug needs an EGFR antibody partner to work in colorectal cancer.
PFS 5.6 vs 2.2 months (960 mg dose, HR 0.49). Approved January 2025.
- Median 5.6 vs 2.2 months with Sotorasib 960 mg + panitumumab compared with Trifluridine-tipiracil or regorafenib; about 3.4 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 51 percent lower chance of the event at any given time (hazard ratio 0.49, likely range 0.3 to 0.8).
- 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.
- 26.4 vs 0 out of 100 had their tumour shrink with Sotorasib 960 mg + panitumumab compared with Trifluridine-tipiracil or regorafenib; 26.4 more per 100.
- Roughly one extra person helped for every 4 treated. That is a rough figure taken from the two percentages, not a guarantee for any one person.
- A response rate counts how many people had their tumours shrink by a set amount; shrinking is encouraging but does not by itself show that people live longer or feel better.
- These results apply to the people the trial enrolled: KRAS G12C colorectal cancer, previously treated: sotorasib + panitumumab vs standard of care. 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.
160 participants enrolled.
| Endpoint | Arm | n | Value | HR (95% CI) | p | Source |
|---|---|---|---|---|---|---|
| Progression-free survival (BICR), sotorasib 960 mg + panitumumabprimary | Sotorasib 960 mg + panitumumab | 53 | 5.6 months | 0.49 (0.3–0.8) | 0.006 | link |
| Trifluridine-tipiracil or regorafenib | 54 | 2.2 months | ||||
| Objective response rate | Sotorasib 960 mg + panitumumab | — | 26.4% | — | — | link |
| Trifluridine-tipiracil or regorafenib | — | 0% |
Patients with KRAS G12C lung cancer that has progressed after chemo-immunotherapy can take an oral KRAS inhibitor instead of docetaxel and gain a somewhat longer time to progression with fewer severe side effects, but should understand that most tumours become resistant within a year and that survival is not improved. KRAS G12C testing is worthwhile, but first-generation inhibitors are a step rather than a cure; combinations and next-generation inhibitors are the active research fronts.
Patients with metastatic colorectal cancer carrying a KRAS G12C mutation (about 3-4% of cases) who have exhausted standard chemotherapy now have a targeted option that works far better than trifluridine-tipiracil or regorafenib. The higher sotorasib dose is clearly superior, and the EGFR antibody is essential because KRAS inhibition alone barely works in bowel cancer. Responses are still modest and short-lived compared with EGFR or ALK inhibitors in lung cancer.