Biomarkers /
KRAS G12C
Back to Biomarkers List
Biomarker-Directed Therapies
KRAS G12C is a predictive biomarker for use of afatinib, dacomitinib, erlotinib, gefitinib, osimertinib, cetuximab, panitumumab, and sotorasib in patients.
Of the therapies with KRAS G12C as a predictive biomarker, 3 are FDA-approved and 7 have NCCN guidelines in at least one clinical setting.
Non-small cell lung carcinoma and colorectal carcinoma have the most therapies targeted against KRAS G12C or its related pathways [5].
Afatinib +
Non-Small Cell Lung Carcinoma -
|
Biomarker Criteria:
Sample must match one or more of the following:
|
Predicted Response: Primary Resistance |
| Clinical Setting(s): Metastatic (NCCN) | |
| Note: According to NCCN, mutations in KRAS have been associated with reduced responsiveness to EGFR TKI therapy. |
|
Biomarker Criteria:
Sample must match all of the following:
Sample must match one or more of the following: Sample must match one or more of the following: |
Predicted Response: Primary Resistance |
| Clinical Setting(s): Metastatic (NCCN) | |
| Note: According to NCCN, mutations in KRAS have been associated with reduced responsiveness to EGFR TKI therapy. |
Cetuximab +
Dacomitinib +
Non-Small Cell Lung Carcinoma -
|
Biomarker Criteria:
Sample must match one or more of the following:
|
Predicted Response: Primary Resistance |
| Clinical Setting(s): Metastatic (NCCN) | |
| Note: According to NCCN, mutations in KRAS have been associated with reduced responsiveness to EGFR TKI therapy. |
|
Biomarker Criteria:
Sample must match all of the following:
Sample must match one or more of the following: Sample must match one or more of the following: |
Predicted Response: Primary Resistance |
| Clinical Setting(s): Metastatic (NCCN) | |
| Note: According to NCCN, mutations in KRAS have been associated with reduced responsiveness to EGFR TKI therapy. |
Erlotinib +
Non-Small Cell Lung Carcinoma -
|
Biomarker Criteria:
Sample must match one or more of the following:
|
Predicted Response: Primary Resistance |
| Clinical Setting(s): Metastatic (NCCN) | |
| Note: According to NCCN, mutations in KRAS have been associated with reduced responsiveness to EGFR TKI therapy. |
|
Biomarker Criteria:
Sample must match all of the following:
Sample must match one or more of the following: Sample must match one or more of the following: |
Predicted Response: Primary Resistance |
| Clinical Setting(s): Metastatic (NCCN) | |
| Note: According to NCCN, mutations in KRAS have been associated with reduced responsiveness to EGFR TKI therapy. |
Gefitinib +
Non-Small Cell Lung Carcinoma -
|
Biomarker Criteria:
Sample must match one or more of the following:
|
Predicted Response: Primary Resistance |
| Clinical Setting(s): Metastatic (NCCN) | |
| Note: According to NCCN, mutations in KRAS have been associated with reduced responsiveness to EGFR TKI therapy. |
|
Biomarker Criteria:
Sample must match all of the following:
Sample must match one or more of the following: Sample must match one or more of the following: |
Predicted Response: Primary Resistance |
| Clinical Setting(s): Metastatic (NCCN) | |
| Note: According to NCCN, mutations in KRAS have been associated with reduced responsiveness to EGFR TKI therapy. |
Osimertinib +
Non-Small Cell Lung Carcinoma -
|
Biomarker Criteria:
Sample must match one or more of the following:
|
Predicted Response: Primary Resistance |
| Clinical Setting(s): Metastatic (NCCN) | |
| Note: According to NCCN, mutations in KRAS have been associated with reduced responsiveness to EGFR TKI therapy. |
|
Biomarker Criteria:
Sample must match all of the following:
Sample must match one or more of the following: Sample must match one or more of the following: |
Predicted Response: Primary Resistance |
| Clinical Setting(s): Metastatic (NCCN) | |
| Note: According to NCCN, mutations in KRAS have been associated with reduced responsiveness to EGFR TKI therapy. |
Panitumumab +
Sotorasib +
Non-Small Cell Lung Carcinoma -
Clinical Trials
KRAS G12C serves as an inclusion eligibility criterion in 25 clinical trials, of which 23 are open and 2 are closed. Of the trials that contain KRAS G12C as an inclusion criterion, 10 are phase 1 (9 open), 9 are phase 1/phase 2 (8 open), 3 are phase 2 (3 open), and 3 are phase 3 (3 open).
Trials with KRAS G12C in the inclusion eligibility criteria most commonly target non-small cell lung carcinoma, malignant solid tumor, colorectal carcinoma, non-squamous non-small cell lung carcinoma, and pancreatic ductal adenocarcinoma [5].
Pembrolizumab, adagrasib, docetaxel, cetuximab, and sotorasib are the most frequent therapies in trials with KRAS G12C as an inclusion criteria [5].
Significance of KRAS G12C in Diseases
Non-Small Cell Lung Carcinoma +
KRAS G12C is an inclusion criterion in 14 clinical trials for non-small cell lung carcinoma, of which 14 are open and 0 are closed. Of the trials that contain KRAS G12C and non-small cell lung carcinoma as inclusion criteria, 5 are phase 1 (5 open), 4 are phase 1/phase 2 (4 open), 3 are phase 2 (3 open), and 2 are phase 3 (2 open) [5].
Sotorasib has evidence of efficacy in patients with KRAS G12C in non-small cell lung carcinoma [5].
Malignant Solid Tumor +
KRAS G12C is an inclusion criterion in 15 clinical trials for malignant solid tumor, of which 13 are open and 2 are closed. Of the trials that contain KRAS G12C and malignant solid tumor as inclusion criteria, 6 are phase 1 (5 open) and 9 are phase 1/phase 2 (8 open) [5].
Colorectal Carcinoma +
KRAS G12C is an inclusion criterion in 7 clinical trials for colorectal carcinoma, of which 7 are open and 0 are closed. Of the trials that contain KRAS G12C and colorectal carcinoma as inclusion criteria, 3 are phase 1 (3 open), 3 are phase 1/phase 2 (3 open), and 1 is phase 3 (1 open) [5].
Pancreatic Ductal Adenocarcinoma +
KRAS G12C is an inclusion criterion in 2 clinical trials for pancreatic ductal adenocarcinoma, of which 2 are open and 0 are closed. Of the trials that contain KRAS G12C and pancreatic ductal adenocarcinoma as inclusion criteria, 1 is phase 1 (1 open) and 1 is phase 1/phase 2 (1 open) [5].
Adenosquamous Lung Carcinoma +
KRAS G12C is an inclusion criterion in 1 clinical trial for adenosquamous lung carcinoma, of which 1 is open and 0 are closed. Of the trial that contains KRAS G12C and adenosquamous lung carcinoma as inclusion criteria, 1 is phase 2 (1 open) [5].
Breast Carcinoma +
KRAS G12C is an inclusion criterion in 1 clinical trial for breast carcinoma, of which 1 is open and 0 are closed. Of the trial that contains KRAS G12C and breast carcinoma as inclusion criteria, 1 is phase 1 (1 open) [5].
Esophageal Squamous Cell Carcinoma +
KRAS G12C is an inclusion criterion in 1 clinical trial for esophageal squamous cell carcinoma, of which 1 is open and 0 are closed. Of the trial that contains KRAS G12C and esophageal squamous cell carcinoma as inclusion criteria, 1 is phase 1 (1 open) [5].
Gastrointestinal Stromal Tumor +
KRAS G12C is an inclusion criterion in 1 clinical trial for gastrointestinal stromal tumor, of which 1 is open and 0 are closed. Of the trial that contains KRAS G12C and gastrointestinal stromal tumor as inclusion criteria, 1 is phase 1 (1 open) [5].
Head And Neck Squamous Cell Carcinoma +
KRAS G12C is an inclusion criterion in 1 clinical trial for head and neck squamous cell carcinoma, of which 1 is open and 0 are closed. Of the trial that contains KRAS G12C and head and neck squamous cell carcinoma as inclusion criteria, 1 is phase 1 (1 open) [5].
Malignant Colorectal Neoplasm +
KRAS G12C is an inclusion criterion in 1 clinical trial for malignant colorectal neoplasm, of which 1 is open and 0 are closed. Of the trial that contains KRAS G12C and malignant colorectal neoplasm as inclusion criteria, 1 is phase 1 (1 open) [5].
Malignant Female Reproductive System Neoplasm +
KRAS G12C is an inclusion criterion in 1 clinical trial for malignant female reproductive system neoplasm, of which 1 is open and 0 are closed. Of the trial that contains KRAS G12C and malignant female reproductive system neoplasm as inclusion criteria, 1 is phase 1 (1 open) [5].
Pancreatic Adenocarcinoma +
KRAS G12C is an inclusion criterion in 1 clinical trial for pancreatic adenocarcinoma, of which 1 is open and 0 are closed. Of the trial that contains KRAS G12C and pancreatic adenocarcinoma as inclusion criteria, 1 is phase 1 (1 open) [5].
Pancreatic Carcinoma +
KRAS G12C is an inclusion criterion in 1 clinical trial for pancreatic carcinoma, of which 1 is open and 0 are closed. Of the trial that contains KRAS G12C and pancreatic carcinoma as inclusion criteria, 1 is phase 1 (1 open) [5].
References
1. Hart R and Prlic A. Universal Transcript Archive Repository. Version uta_20180821. San Francisco CA: Github;2015. https://github.com/biocommons/uta
2. The UniProt Consortium. UniProt: a worldwide hub of protein knowledge. Nucleic Acids Research. 2019;47:D506-D515.
3. Liu X, Wu C, Li C, and Boerwinkle E. dbNSFP v3.0: A one-stop database of functional predictions and annotations for human nonsynonymous and splice site SNVs. Human Mutation. 2015;37:235-241.
Liu X, Jian X, and Boerwinkle E. dbNSFP: A lightweight database of human nonsynonymous SNPs and their functional predictions. Human Mutation. 2011;32:894-899.
4. The AACR Project GENIE Consortium. AACR Project GENIE: powering precision medicine through an international consortium. Cancer Discovery. 2017;7(8):818-831. Dataset Version 8. This dataset does not represent the totality of the genetic landscape; see paper for more information.
5. All assertions and clinical trial landscape data are curated from primary sources. You can read more about the curation process here.
