INDICATION

LUMAKRAS® is indicated for the treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC), as determined by an FDA-approved test, who have received at least one prior systemic therapy.

This indication is approved under accelerated approval based on overall response rate (ORR) and duration of response (DOR). Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).
NSCLC
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Prevalence Testing for KRAS G12C How to test

Prevalence

~ 13% of patients with non-squamous NSCLC have an actionable KRAS G12C mutation1

Prevalence of oncogenic drivers in non-squamous NSCLC1,*
Pie chart highlighting KRAS G12C as 13% of oncogenic drivers in lung cancer. EGFR is 20%, with other biomarkers totaling 45%. Other is 55% Pie chart highlighting KRAS G12C as 13% of oncogenic drivers in lung cancer. EGFR is 20%, with other biomarkers totaling 45%. Other is 55%

  • KRAS mutations—including KRAS G12C—do not typically overlap with other driver mutations and are truncal in nature2

  • Nearly 45% of patients with NSCLC have an actionable oncogenic driver with KRAS G12C and the other 9 actionable biomarkers1,3,†

*Molecular alteration prevalence can vary slightly between different datasets and studies. Values in graph based on approximate molecular alteration frequencies from the AACR GENIE version 12.0 dataset (N=19,777). Participating institutions include academic centers in Western countries. This graph only includes alterations predictive of response to an FDA-approved drug in locally advanced or metastatic NSCLC.1

†As of August 27, 2024.3

AACR, American Association for Cancer Research; ALK, anaplastic lymphoma kinase; BRAF, v-Raf murine sarcoma viral oncogene homolog B; EGFR, epidermal growth factor receptor; KRAS, Kirsten rat sarcoma viral oncogene homolog; METex14, mesenchymal-epithelial transition exon 14; NRG1, neuregulin 1; NSCLC, non-small cell lung cancer; NTRK, neurotrophic tyrosine receptor kinase; RET, rearranged during transfection; ROS1, rearrangement of the receptor tyrosine kinase 1.

Testing for KRAS G12C
nccn guidelines testing
NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) recommend testing all eligible patients with advanced NSCLC for actionable mutations, including KRAS, EGFR, ALK, ROS1, BRAF, NTRK1/2/3, METex14 skipping, RET, NRG1, and HER2 (IHC)4,*,†,‡,§

Complete genotyping for KRAS, EGFR, ALK, ROS1, BRAF, NTRK1/2/3, METex14 skipping, RET, NRG1, and HER2 (IHC), via biopsy and/or plasma testing should be done

Biomarker testing in NSCLC may be underutilized in certain populations5,6

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In a real-world database of 7,627 patients diagnosed with NSCLC on or after January 1, 2017, biomarker testing was underutilized among Black/African American patients6,**

Black/African American

White††

Testing before first-line therapy

29.7%
(n=922)

vs

36.6%
(n=6,705)

Testing anytime after diagnosis

43.8%
(n=922)

vs

54.7%
(n=6,705)
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While KRAS mutations are most commonly found in smokers, they can occur regardless of smoking status or clinical or demographic characteristics7

Help ensure all patients have access to precision medicine and appropriate targeted therapies. Test all eligible patients for the KRAS G12C mutation

*The NCCN Guidelines for NSCLC provide recommendations for individual biomarkers that should be tested and recommend testing techniques but do not endorse any specific commercially available biomarker assays or commercial laboratories.4

†It is recommended at this time that, when feasible, testing be performed via a broad, panel-based approach.4

‡Does not include locally advanced.4

§Testing for HER2 via IHC is recommended at some point during progression. Timing should be balanced with tissue conservation.4

**This study used the Flatiron EHR-derived deidentified database to evaluate a total of 10,333 patients with an advanced/metastatic non-squamous NSCLC diagnosis on or after January 1, 2017. 7,627 patients were White (n=6,705) or of Black/African American (n=922) descent. The study included patients who received treatment within 120 days, and excluded patients with additional cancers and those who died within 120 days of diagnosis. Biomarker testing included ALK, EGFR, ROS1, KRAS, and BRAF and included all single-gene and NGS-based tests, and was evaluated within 10 days of advanced/metastatic diagnosis.6

††Race and ethnicity were patient self-reported variables.

ALK, anaplastic lymphoma kinase; BRAF, v-Raf murine sarcoma viral oncogene homolog B; EGFR, epidermal growth factor receptor; EHR, electronic health record; HER2, human epidermal growth factor receptor 2; IHC, immunohistochemistry; KRAS, Kirsten rat sarcoma viral oncogene homolog; MET, mesenchymal epithelial transition; NCCN, National Comprehensive Cancer Network; NRG1, neuregulin 1; NSCLC, non-small cell lung cancer; NTRK, neurotrophic-tropomyosin receptor kinase; RET, rearranged during transfection; ROS1, rearrangement of the receptor tyrosine kinase 1.

 

How to test

KRAS G12C can be detected in tissue and liquid biopsy specimens using well-validated common molecular testing methods.8,9

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Check your current NGS panel—most already include KRAS G12C9

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Tissue biopsy is the gold standard for biomarker testing; however, using cfDNA in addition to tissue resulted in a 48% increase in the identification of patients with a guideline-recommended biomarker8,*

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Liquid biopsy may identify actionable mutations like KRAS G12C when tissue quantity is not sufficient10,11

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Because of variable tumor shedding and assay sensitivity, confirming negative liquid biopsy results with tissue biopsy is recommended as mutations cannot be ruled out from a liquid sample alone10

*In the NILE study of 282 patients with non-squamous mNSCLC who received SOC tissue genotyping and cfDNA analysis for guideline-recommended biomarkers, including KRAS, between 2016 and 2018. Overall concordance across four genes (EGFR exon 19 deletion and L858R, ALK fusion, ROS1 fusion, and BRAF V600E) was >98.2% with a positive predictive value of 100%.8

FDA-approved tissue and liquid companion diagnostics are available to test for KRAS G12C†

QIAGEN logo
Tissue PCR

www.qiagen.com/KRAS

Download QIAGEN therascreen® KRAS RGQ PCR Kit
Guardant360 CDx logo
Liquid NGS

www.guardant360cdx.com

Download Guardant360® CDx

†Information on FDA-approved tests can be found at https://www.fda.gov/medical-devices/products-and-medical-procedures/vitro-diagnostics.

Call your lab and ask about your patients' KRAS G12C status.

There are differences in how reports may list KRAS G12C.12,13

Observation

There are various ways that KRAS G12C mutations can be reported, such as 12Cys, Gly12Cys (GGT or TGT), c.34G>T, or p.G12C.

Suggestion

For ease of interpretation, consider noting KRAS G12C in the synopsis of your report.

Example biomarker report showing different ways KRAS G12C may be listed Example biomarker report showing different ways KRAS G12C may be listed

Keep test results text-searchable and within an EMR so patients' biomarker results are easily accessible when looking back following 1L treatment.

1L, first line; ALK, anaplastic lymphoma kinase; BRAF, v-Raf murine sarcoma viral oncogene homolog B; CDx, companion diagnostic; cfDNA, circulating free DNA; EGFR, epidermal growth factor receptor; EMR, electronic medical record; KRAS, Kirsten rat sarcoma viral oncogene homolog; mNSCLC, metastatic non-small cell lung cancer; NGS, next-generation sequencing; PCR, polymerase chain reaction; ROS1, rearrangement of the receptor tyrosine kinase 1; SOC, standard-of-care.

Learn about LUMAKRAS®

IMPORTANT SAFETY INFORMATION

Hepatotoxicity

  • LUMAKRAS® can cause hepatotoxicity and increased ALT or AST which may lead to drug-induced liver injury and hepatitis.
  • In the pooled safety population of NSCLC patients who received single agent LUMAKRAS® 960 mg hepatotoxicity occurred in 27% of patients, of which 16% were Grade ≥ 3. Among patients with hepatotoxicity who required dosage modifications, 64% required treatment with corticosteroids.
  • In this pooled safety population of NSCLC patients who received single agent LUMAKRAS® 960 mg, 17% of patients who received LUMAKRAS® had increased alanine aminotransferase (ALT)/increased aspartate aminotransferase (AST); of which 9% were Grade ≥ 3. The median time to first onset of increased ALT/AST was 6.3 weeks (range: 0.4 to 42). Increased ALT/AST leading to dose interruption or reduction occurred in 9% of patients treated with LUMAKRAS®. LUMAKRAS® was permanently discontinued due to increased ALT/AST in 2.7% of patients. Drug-induced liver injury occurred in 1.6% (all grades) including 1.3% (Grade ≥ 3).
  • In this pooled safety population of NSCLC patients who received single agent LUMAKRAS® 960 mg, a total of 40% patients with recent (≤ 3 months) immunotherapy prior to starting LUMAKRAS® had an event of hepatotoxicity. An event of hepatotoxicity was observed in 18% of patients who started LUMAKRAS® more than 3 months after last dose of immunotherapy and in 17% of those who never received immunotherapy. Regardless of time from prior immunotherapy, 94% of hepatotoxicity events improved or resolved with dosage modification of LUMAKRAS®, with or without corticosteroid treatment.
  • Monitor liver function tests (ALT, AST, alkaline phosphatase, and total bilirubin) prior to the start of LUMAKRAS®, every 3 weeks for the first 3 months of treatment, then once a month or as clinically indicated, with more frequent testing in patients who develop transaminase and/or bilirubin elevations. Withhold, reduce the dose or permanently discontinue LUMAKRAS® based on severity of the adverse reaction. Consider administering systemic corticosteroids for the management of hepatotoxicity.

Interstitial Lung Disease (ILD)/Pneumonitis

  • LUMAKRAS® can cause ILD/pneumonitis that can be fatal.
  • In the pooled safety population of NSCLC patients who received single agent LUMAKRAS® 960 mg ILD/pneumonitis occurred in 2.2% of patients, of which 1.1% were Grade ≥ 3, and 1 case was fatal. The median time to first onset for ILD/pneumonitis was 8.6 weeks (range: 2.1 to 36.7 weeks). LUMAKRAS® was permanently discontinued due to ILD/pneumonitis in 1.3% of LUMAKRAS®-treated patients. Monitor patients for new or worsening pulmonary symptoms indicative of ILD/pneumonitis (e.g., dyspnea, cough, fever). Immediately withhold LUMAKRAS® in patients with suspected ILD/pneumonitis and permanently discontinue LUMAKRAS® if no other potential causes of ILD/pneumonitis are identified.

Most Common Adverse Reactions

  • The most common adverse reactions ≥ 20% were diarrhea, musculoskeletal pain, nausea, fatigue, hepatotoxicity, and cough.

Drug Interactions

  • Advise patients to inform their healthcare provider of all concomitant medications, including prescription medicines, over‑the‑counter drugs, vitamins, dietary and herbal products.
  • Inform patients to avoid proton pump inhibitors and H2 receptor antagonists while taking LUMAKRAS®.
  • If coadministration with an acid-reducing agent cannot be avoided, inform patients to take LUMAKRAS® 4 hours before or 10 hours after a locally acting antacid.

INDICATION

LUMAKRAS® is indicated for the treatment of adult patients with KRAS G12C‑mutated locally advanced or metastatic non‑small cell lung cancer (NSCLC), as determined by an FDA‑approved test, who have received at least one prior systemic therapy.

This indication is approved under accelerated approval based on overall response rate (ORR) and duration of response (DOR). Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

 

Please see full LUMAKRAS® Prescribing Information.

  • References: 1. Data on file, Amgen; [Analysis of AACR Genie v13]. 2. Skoulidis F, et al. Nat Rev Cancer. 2019;19:495–509. 3. American Cancer Society. www.cancer.org. Accessed July 2, 2025. 4. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer v.7.2025. © National Comprehensive Cancer Network, Inc. 2025. All rights reserved. Accessed July 10, 2025. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way. 5. Hess LM, et al. JTO Clin Res Rep. 2022;3:100336. 6. Bruno DS, et al. JCO Precis Oncol. 2022;6:e2100427. 7. Aggarwal S, et al. Presented at: The European Society for Medical Oncology; September 19–21, 2020; Virtual Congress. 8. Leighl NB, et al. Clin Cancer Res. 2019;25:4691–4700. 9. Sherwood JL, et al. ESMO Open. 2017;2:e000235. 10. Rolfo C, et al. J Thorac Oncol. 2021;16:1647–1662. 11. Rolfo C, et al. J Thorac Oncol. 2018;13:1248–1268. 12. Baskovich BW, et al. College of American Pathologists. https://documents.cap.org/protocols/PleuraPericard_4.1.0.0.REL_CAPCP.pdf. Accessed July 2, 2025. 13. Cavagna R, et al. JCO Glob Oncol. 2021;7:639–645.