They continue to regenerate every 24-48 hours 1-3


The regeneration of KRAS G12C needs to be continuously inhibited.

KRAS G12C shown to decrease likelihood of survival4-6

A study of advanced NSCLC showed that KRAS G12C is associated with a significantly shorter overall survival compared with other KRAS mutations (6.4 vs 10.3 months) and wild-type KRAS (16.1 months, P=0.011).4*

Click the chart to enlarge

Adapted by permission from the International Institute of Anticancer Research: Anticancer Res. 2016;36:1077-1082. © 2016.

Median OS KRAS G12C: 6.4 months

Median OS OtherKRAS: 10.3 months

Median OS Wild-typeKRAS: 16.1 months

The study was a retrospective analysis of patients (N=127) with advanced NSCLC who received chemotherapy at second- or third-line therapy. Overall survival was significantly longer for patients with wild-type KRAS vs those with KRAS mutations (16.1 vs 7.2 months, P=0.008).4

KRAS mutation-driven disease is associated with higher likelihood of brain metastases7-9

In some tumor types, KRAS mutations are associated with higher likelihood of brain metastases.8,9

  • According to one study, KRAS mutations are prevalent in brain metastasis9*

    Distribution of KRAS Mutations in Patients With Brain Metastasis9*

    - In that same study, the presence of a RAS mutation increases the risk of a brain metastasis by 3.7X9*

Cumulative incidence from date of first metastasis. The study was an analysis of electronic medical records for metastatic colorectal cancer of patients (N=918) genotyped for RAS status at a single institution between 2008 to 2012.9

KRAS G12C is a meaningful problem in NSCLC

  • The most common KRAS mutation in NSCLC is G12C10,11

  • KRAS G12C accounts for ~50% of all KRAS mutations—more than ALK, ROS1, RET and TRK 1/2/3 combined12

  • 1 in 8 patients with NSCLC are positive for a KRAS G12C mutation13,14

KRAS G12C mutations: Associated with aggressive growth10,15,16

When KRAS mutations occur, it pushes the cell towards unregulated growth or tumorigenesis and disease progression.10,15,16

The KRAS G12C mutation locks the protein in the active “on” state16-18

KRAS G12C functions as a molecular on/off switch.16-18

When the protein turns “on” it activates downstream cell signaling pathways for growth and survival.17,18

Is it enough to turn "off" KRAS G12C through direct inhibition?

The unique confirmation of KRAS G12C provides the opportunity for a binding pocket for small molecules, which potentially lock the protein in an inactive state.19-21

Targeting KRAS G12C can cause tumors to shrink or die.20,21

The regeneration of KRAS G12C needs to be continuously inhibited.

KRAS G12C proteins continue to regenerate every 24-48 hours.1-3
It's not enough to just turn it off. Even with direct inhibition,
proliferation may still be a problem.