- Design
- Multicentre phase 1b/2 trial with open-label randomised phase 2 cohort
- Population
- 51 patients with previously treated KRAS G12C metastatic colorectal cancer (China)
- Primary outcome
- Investigator-assessed objective response rate
- Effect
- Randomised: 38.9% vs 16.7%; difference 22.2% (95% CI −7.7 to 49.1), one-sided p = 0.068
This Chinese phase 1b/2 study tested ifebemtinib, an oral focal adhesion kinase (FAK) inhibitor, with the KRAS G12C inhibitor garsorasib in previously treated metastatic colorectal cancer carrying KRAS G12C. After a single-arm phase (15 patients, response 46.7%), 36 patients were randomised to the combination or garsorasib alone.
Confirmed objective response was 38.9% with the combination against 16.7% with garsorasib alone (difference 22.2%, 95% CI −7.7 to 49.1; one-sided p = 0.068). Grade 3 treatment-related adverse events occurred in 33% vs 28%, mainly diarrhoea; there were no treatment-related deaths.
KRAS G12C inhibitors alone work poorly in colorectal cancer because of feedback signalling, and current practice pairs them with an EGFR antibody. This is an alternative partner with a promising signal, but the numbers are too small to draw conclusions. Funders included InxMed and InventisBio as well as public research bodies.
- Test for KRAS G12C in metastatic colorectal cancer; it opens targeted options.
- KRAS G12C inhibitors are paired with a second agent in colorectal cancer; monotherapy responses are low.
- Ifebemtinib plus garsorasib is investigational and not available outside trials.
- Watch for diarrhoea, the main grade 3 toxicity of the combination.
Why it matters
It points to a possible all-oral combination for KRAS G12C colorectal cancer.
Don't overread it
This small phase 2 randomised comparison did not reach statistical significance.
The statistics, in plain English
With 18 patients per arm, a difference of 22 percentage points has a 95% CI from about −8 to +49, so it could be chance. Response rate is also a surrogate for survival.
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