Background
Adagrasib, also called “Krazati”, is a tablet taken by mouth which inhibits KRAS G12C mutation. It has shown clinical activity in pretreated patients with several tumor types, including colorectal cancer.
Combining a KRAS G12C inhibitor with an Epidermal Growth Factor Receptor, EGFR, antibody such as Erbitux could be effective.
On 12 December 2022, the US Food and Drug Administration (FDA) granted accelerated approval to Krazati for adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with KRAS G12C-mutation.
Methods of the Study
In this phase 1–2 clinical trial, heavily pretreated patients were assigned with metastatic colorectal cancer with mutant KRAS G12C to receive Krazati monotherapy (600 mg orally twice daily) or Krazati (at the same dose) in combination with intravenous Cetuximab once a week or every 2 weeks.
The primary end points were objective response which is the decrease in tumor size and safety.
Results
As of June 16, 2022, a total of 44 patients with colorectal cancer had received Krazati, and 32 had received combination therapy with Krazati and Erbitux.
It is important to note that the KRAS G12C mutation is common in only 3.05% of all colorectal cancer patients.
In the monotherapy group a response was reported in 19% of the patients.
The median response duration was 4.3 months.
The median Progression-Free Survival, which is the length of time until disease progression, was 5.6 months.
In the combination-therapy group, 46% of the patients responded to the treatment.
The median response duration was 7.6 months.
The median Progression-Free Survival was 6.9 months.
The percentage of harsh treatment-related side effects was 34% in the monotherapy group and 16% in the combination-therapy group.
No deaths were observed.
Conclusions
Krazati had antitumor activity in heavily pretreated patients with metastatic colorectal cancer with mutant KRAS G12C, both as oral monotherapy and in combination with Erbitux.
The median response duration was more than 6 months in the combination-therapy group.
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