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    BIOMARKER:

    KRAS exon 4 mutation

    i
    Other names: KRAS, KRAS1, KRAS2, Kirsten rat sarcoma viral oncogene homolog
    Entrez ID:
    3845
    Related biomarkers:
    Expression
    Mutation
    CNA
    Others
    Related tests:
    1d
    Liquid Biopsy in Next Generation Sequencing (NGS) for tumor molecular profiling in advanced NSCLC in Umbria population: a realworld experience (AIOM 2024)
    Blood-based LB performed by NGS is a non-invasive viable alternative tool for molecular genotyping and identifiy tumor-derived somatic alterations to increase the number of pts elegible to target therapy and guide personalized medicine.
    Clinical • Real-world evidence • Liquid biopsy • Next-generation sequencing • Real-world • Metastases • Biopsy
    |
    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • MET (MET proto-oncogene, receptor tyrosine kinase) • RET (Ret Proto-Oncogene)
    |
    TP53 mutation • BRAF V600E • KRAS mutation • EGFR mutation • KRAS G12C • BRAF V600 • RET fusion • MET exon 14 mutation • KRAS G12 • KRAS exon 4 mutation
    |
    Oncomine™ Pan-Cancer Cell-Free Assay
    5ms
    MTAP deficiency by immunohistochemistry as a new potentially predictive marker in non-small-cell lung cancer (NSCLC) (ECP 2024)
    20% of NSCLC in our cohort show MTAP deficiency by IHC. IHC is more sensitive than targeted panel-based NGS to detect MTAP deficiency in NSCLC. The results of ongoing analyses to explore reasons for the lower sensitivity of NGS will be presented at the congress.
    PD(L)-1 Biomarker • IO biomarker
    |
    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • MET (MET proto-oncogene, receptor tyrosine kinase) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MTAP (Methylthioadenosine Phosphorylase)
    |
    PD-L1 expression • TP53 mutation • KRAS mutation • EGFR mutation • BRAF mutation • HER-2 mutation • HER-2 expression • KRAS exon 4 mutation
    |
    Oncomine Precision Assay
    8ms
    STRATEGIC-1: Multi-Line Therapy Trial in Unresectable Metastatic Colorectal Cancer (clinicaltrials.gov)
    P3, N=464, Active, not recruiting, GERCOR - Multidisciplinary Oncology Cooperative Group | Recruiting --> Active, not recruiting | Trial completion date: Jun 2021 --> Dec 2024 | Trial primary completion date: Jun 2021 --> Jul 2023
    Enrollment closed • Trial completion date • Trial primary completion date • Metastases
    |
    KRAS (KRAS proto-oncogene GTPase) • NRAS (Neuroblastoma RAS viral oncogene homolog)
    |
    NRAS mutation • KRAS wild-type • RAS mutation • RAS wild-type • NRAS wild-type • KRAS exon 3 mutation • KRAS exon 4 mutation
    |
    Avastin (bevacizumab) • Erbitux (cetuximab) • 5-fluorouracil • Vectibix (panitumumab) • capecitabine • oxaliplatin • irinotecan • leucovorin calcium
    9ms
    Comparative analysis of KRAS4a and KRAS4b splice variants reveals distinctive structural and functional properties. (PubMed, Sci Adv)
    Notably, KRAS4a exhibits substantial transcript abundance in bile ducts, liver, and stomach, with transcript levels approaching KRAS4b in the colon and rectum. Functional disparities were observed in full-length KRAS variants, highlighting the impact of HVR variations on interaction with trafficking proteins and downstream effectors like RAF and PI3K within cells.
    Journal
    |
    KRAS (KRAS proto-oncogene GTPase) • RAF1 (Raf-1 Proto-Oncogene Serine/Threonine Kinase)
    |
    KRAS mutation • KRAS exon 4 mutation
    9ms
    SWOG S1613: S1613, Trastuzumab and Pertuzumab or Cetuximab and Irinotecan Hydrochloride in Treating Patients With Locally Advanced or Metastatic HER2/Neu Amplified Colorectal Cancer That Cannot Be Removed by Surgery (clinicaltrials.gov)
    P2, N=240, Active, not recruiting, SWOG Cancer Research Network | Trial completion date: Jun 2024 --> Nov 2024
    Trial completion date • Surgery • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog)
    |
    BRAF V600E • HER-2 amplification • BRAF V600 • KRAS exon 4 mutation • BRAF exon 15 mutation
    |
    Herceptin (trastuzumab) • Erbitux (cetuximab) • Perjeta (pertuzumab) • irinotecan • Trazimera (trastuzumab-qyyp)
    1year
    Molecular Pattern and Clinical Implications of KRAS/NRAS and BRAF Mutations in Colorectal Cancer. (PubMed, Curr Issues Mol Biol)
    NRAS and BRAF mutations were significantly more frequent in the right colon. BRAF mutation was more common in women and in the right colon.
    Journal
    |
    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog) • RAS (Rat Sarcoma Virus)
    |
    BRAF V600E • KRAS mutation • BRAF mutation • NRAS mutation • KRAS G12D • RAS mutation • KRAS G12 • KRAS exon 2 mutation • NRAS G12D • KRAS exon 3 mutation • KRAS exon 4 mutation
    1year
    KRAS Mutation Status in Bulgarian Patients with Advanced and Metastatic Colorectal Cancer. (PubMed, Int J Mol Sci)
    Studying the link between tumor location and KRAS mutations in exon 4 is crucial for better characterizing CRC patients. Further research with larger cohorts, especially in rectal cancer patients, could provide valuable insights for patient follow-up and treatment selection.
    Journal • Metastases
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS mutation • RAS mutation • KRAS exon 4 mutation
    over1year
    FOLFOXIRI Plus Panitumumab in Metastatic RAS Wild-type, Left-sided Colorectal Cancer (clinicaltrials.gov)
    P2, N=27, Active, not recruiting, Criterium, Inc. | Recruiting --> Active, not recruiting | Trial completion date: Mar 2023 --> Jan 2025 | Trial primary completion date: Mar 2023 --> Dec 2024
    Enrollment closed • Trial completion date • Trial primary completion date • Metastases
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS wild-type • RAS wild-type • KRAS exon 2 mutation • KRAS exon 2 wild-type • KRAS exon 3 mutation • KRAS exon 4 mutation
    |
    5-fluorouracil • Vectibix (panitumumab) • oxaliplatin • irinotecan • leucovorin calcium
    over1year
    Comprehensive Pneumonitis Assessment Among Inoperable Stage III NSCLC Patients Treated with Chemoradiotherapy-Immunotherapy Regimen (IASLC-WCLC 2023)
    Our institutional experience showed that adjuvant Durvalumab improved PFS in both cCRT and sCRT. In multivariate analysis, Durvalumab and cCRT (compared to sCRT) were found to be independent prognostic factors associated with increased risk of pneumonitis. These results are comparable to the Pacific trial.
    Clinical • PD(L)-1 Biomarker • IO biomarker
    |
    EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • MET (MET proto-oncogene, receptor tyrosine kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
    |
    KRAS mutation • EGFR mutation • KRAS G12C • MET exon 14 mutation • MET mutation • KRAS G12 • KRAS exon 4 mutation
    |
    Imfinzi (durvalumab)
    over1year
    FOLFOXIRI With or Without Panitumumab in Metastatic Colorectal Cancer (VOLFI) (clinicaltrials.gov)
    P2, N=93, Completed, AIO-Studien-gGmbH | Active, not recruiting --> Completed
    Trial completion • Metastases
    |
    EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • NRAS (Neuroblastoma RAS viral oncogene homolog) • PTEN (Phosphatase and tensin homolog) • ERCC1 (Excision repair cross-complementation group 1) • RAS (Rat Sarcoma Virus) • MTHFR (Methylenetetrahydrofolate Reductase)
    |
    EGFR mutation • PIK3CA mutation • KRAS wild-type • RAS wild-type • EGFR exon 18 mutation • KRAS exon 2 mutation • EGFR mutation + PIK3CA mutation • KRAS exon 2 wild-type • KRAS exon 3 mutation • KRAS exon 4 mutation
    |
    5-fluorouracil • Vectibix (panitumumab) • oxaliplatin • irinotecan • leucovorin calcium
    over1year
    Landscape of KRAS, BRAF, and PIK3CA Mutations and Clinical Features of EBV-Associated and Microsatellite Unstable Gastric Cancer (PubMed, Mol Biol (Mosk))
    The EBV^(+) subtype was associated with better prognosis. The five-year survival rates were 100.0 and 54.7% for MSI and EBV^(+) GCs, respectively.
    Journal
    |
    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)
    |
    BRAF V600E • KRAS mutation • BRAF mutation • PIK3CA mutation • BRAF V600 • PIK3CA E545K • PIK3CA E545 • KRAS exon 3 mutation • KRAS exon 4 mutation
    over1year
    Prognostic Value of KRAS Exon-specific Mutations in Patients With Colorectal Cancer. (PubMed, Anticancer Res)
    In stage I-III CRC patients, KRAS exon 2 mutations had the worst prognosis, whereas KRAS wild type, exon 3 mutations, exon 4 mutations, and NRAS mutations had better prognoses.
    Journal
    |
    KRAS (KRAS proto-oncogene GTPase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • RAS (Rat Sarcoma Virus)
    |
    KRAS mutation • NRAS mutation • KRAS wild-type • RAS mutation • RAS wild-type • KRAS exon 2 mutation • KRAS exon 3 mutation • KRAS exon 4 mutation
    over1year
    Prognostic factors for overall survival, recurrence-free survival, and metastasis-free survival of colon cancer in Morocco (AACR 2023)
    However, the type of mutated exon had no prognostic impact on either.Conclusion In our setting right location, localized stage, absence of metastatic nodes, MSI status and mutated status of exon 4 of the KRAS gene (compared to other exons) are all predictive factors of better overall survival of colon cancer in Morocco. The type of the mutated exon of the RAS genes has no impact on RFS and MFS.
    Clinical
    |
    KRAS (KRAS proto-oncogene GTPase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • MSI (Microsatellite instability) • RAS (Rat Sarcoma Virus)
    |
    KRAS mutation • NRAS mutation • RAS mutation • KRAS exon 4 mutation
    almost2years
    Cetuximab Plus FOLFOXIRI vs Cetuximab Plus FOLFOX For CRCLM (clinicaltrials.gov)
    P2, N=176, Completed, Sun Yat-sen University | Recruiting --> Completed
    Trial completion
    |
    KRAS (KRAS proto-oncogene GTPase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • RAS (Rat Sarcoma Virus)
    |
    KRAS wild-type • RAS wild-type • KRAS exon 2 mutation • KRAS exon 2 wild-type • KRAS exon 3 mutation • KRAS exon 4 mutation
    |
    Erbitux (cetuximab) • 5-fluorouracil • oxaliplatin • irinotecan • leucovorin calcium
    almost2years
    A Study to Find a Safe and Effective Dose of BI 1701963 Alone and in Combination With BI 3011441 in Patients With Advanced Cancer and a Certain Mutation (Kirsten Rat Sarcoma Viral Oncogene Homologue [KRAS]) (clinicaltrials.gov)
    P1, N=8, Terminated, Boehringer Ingelheim | Completed --> Terminated; Sponsor decision
    Preclinical • Trial termination • Combination therapy • Metastases
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS mutation • KRAS G12 • KRAS G13 • KRAS A146 • KRAS Q61 • KRAS A59 • KRAS K117 • KRAS exon 4 mutation
    |
    LNP3794 • BI 1701963
    almost2years
    SWOG S1613: S1613, Trastuzumab and Pertuzumab or Cetuximab and Irinotecan Hydrochloride in Treating Patients With Locally Advanced or Metastatic HER2/Neu Amplified Colorectal Cancer That Cannot Be Removed by Surgery (clinicaltrials.gov)
    P2, N=240, Active, not recruiting, Southwest Oncology Group | Trial primary completion date: Nov 2023 --> Nov 2022
    Trial primary completion date • Surgery • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog)
    |
    BRAF V600E • HER-2 amplification • BRAF V600 • KRAS exon 4 mutation • BRAF exon 15 mutation
    |
    Herceptin (trastuzumab) • Erbitux (cetuximab) • Perjeta (pertuzumab) • irinotecan • Trazimera (trastuzumab-qyyp)
    almost2years
    A Study of Tucatinib and Trastuzumab in People With Rectal Cancer (clinicaltrials.gov)
    P2, N=37, Recruiting, Memorial Sloan Kettering Cancer Center
    New P2 trial • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase)
    |
    HER-2 positive • HER-2 overexpression • HER-2 amplification • RAS wild-type • KRAS exon 2 mutation • RAS wild-type + HER-2 positive • KRAS exon 3 mutation • KRAS exon 4 mutation
    |
    Herceptin (trastuzumab) • Tukysa (tucatinib)
    almost2years
    A Study to Find a Safe and Effective Dose of BI 1701963 Alone and in Combination With BI 3011441 in Patients With Advanced Cancer and a Certain Mutation (Kirsten Rat Sarcoma Viral Oncogene Homologue [KRAS]) (clinicaltrials.gov)
    P1, N=8, Completed, Boehringer Ingelheim | Terminated --> Completed
    Trial completion
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS mutation • KRAS G12 • KRAS G13 • KRAS A146 • KRAS Q61 • KRAS A59 • KRAS K117 • KRAS exon 4 mutation
    |
    LNP3794 • BI 1701963
    almost2years
    Mutations matter: An observational study of the prognostic and predictive value of KRAS mutations in metastatic colorectal cancer. (PubMed, Front Oncol)
    Treatment with bevacizumab (BV) increased significatively mPFS (p=0.036) and mOS (p=0.019) of the entire population with a substantial benefit in mOS for G12V mutation (p=0.031). Patterns of presentation and prognosis among patients with specific RAS hotspot mutations deserve to be extensively studied in large datasets, with a specific attention to the uncommon isoforms and the role of anti-angiogenic drugs.
    Observational data • Journal
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS mutation • KRAS G12C • KRAS G12D • KRAS G12V • RAS mutation • KRAS G12 • KRAS exon 4 mutation
    |
    Avastin (bevacizumab)
    almost2years
    Mutation status of full RAS and BRAF in 169 Moroccan patients with colorectal cancer. (ASCO-GI 2023)
    Beside established anti-CRC treatment, better understanding of the causality of CRC can be established by combining epidemiology and genetic/epigenetic on CRC etiology in Morocco. This approach may be able to significantly reduce the burden of disease in the country. Moreover, the Moroccan government should develop policy on CRC prevention and public health programs which may serve as a feasible setting to increase public awareness on lifestyle risk factors.
    Clinical
    |
    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog) • RAS (Rat Sarcoma Virus)
    |
    BRAF V600E • KRAS mutation • KRAS G12C • BRAF mutation • NRAS mutation • BRAF V600 • KRAS G12D • RAS mutation • NRAS Q61K • KRAS G12 • NRAS Q61 • KRAS exon 2 mutation • NRAS G12D • NRAS G13 • KRAS exon 3 mutation • KRAS exon 4 mutation • KRAS Q61K
    |
    Idylla™ BRAF Mutation Test • Idylla™ KRAS Mutation Test
    almost2years
    SWOG S1613: S1613, Trastuzumab and Pertuzumab or Cetuximab and Irinotecan Hydrochloride in Treating Patients With Locally Advanced or Metastatic HER2/Neu Amplified Colorectal Cancer That Cannot Be Removed by Surgery (clinicaltrials.gov)
    P2, N=240, Active, not recruiting, Southwest Oncology Group | Trial completion date: Jun 2023 --> Jun 2024 | Trial primary completion date: Nov 2022 --> Nov 2023
    Trial completion date • Trial primary completion date • Surgery • Metastases
    |
    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog)
    |
    BRAF V600E • HER-2 amplification • BRAF V600 • KRAS exon 4 mutation • BRAF exon 15 mutation
    |
    Herceptin (trastuzumab) • Erbitux (cetuximab) • Perjeta (pertuzumab) • irinotecan • Trazimera (trastuzumab-qyyp)
    almost2years
    FOLFOXIRI Plus Panitumumab in Metastatic RAS Wild-type, Left-sided Colorectal Cancer (clinicaltrials.gov)
    P2, N=35, Recruiting, Criterium, Inc. | Trial completion date: Dec 2022 --> Mar 2023 | Trial primary completion date: Sep 2022 --> Mar 2023
    Trial completion date • Trial primary completion date • Metastases
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS wild-type • RAS wild-type • KRAS exon 2 mutation • KRAS exon 2 wild-type • KRAS exon 3 mutation • KRAS exon 4 mutation
    |
    5-fluorouracil • Vectibix (panitumumab) • oxaliplatin • irinotecan • leucovorin calcium
    2years
    Prevalence and patterns of mutations in RAS/RAF/MEK/ERK/MAPK signaling pathway in colorectal cancer in North Africa. (PubMed, BMC Cancer)
    KRAS mutated CRC patients in North Africa have been identified with incidence closer to the European figures. Beside established anti-CRC treatment, better understanding of the causality of CRC can be established by combining epidemiology and genetic/epigenetic on CRC etiology. This approach may be able to significantly reduce the burden of CRC in North Africa.
    Review • Journal
    |
    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog)
    |
    KRAS mutation • KRAS G12C • BRAF mutation • NRAS mutation • KRAS G12D • KRAS G12V • RAS mutation • KRAS G12A • KRAS G12 • NRAS Q61 • KRAS G12S • KRAS exon 2 mutation • NRAS G12D • NRAS G13 • NRAS Q61L • KRAS A59T • KRAS A146T • NRAS A146T • NRAS G13R • KRAS A146V • KRAS G13C • KRAS exon 3 mutation • KRAS exon 4 mutation • NRAS A146 • NRAS A59 • KRAS Q61L • NRAS G12S • KRAS A146P
    2years
    Prognosis and Efficacy of Adjuvant Therapy in Post-Surgical NSCLC Patients with WES-Based Genetic Profiling (IASLC-ACLC 2022)
    [Conclusion] Compared with the PN group, pts with EGFR MT and RET fusion tended to have a better RFS and patients with EGFR MT, ALK fusion, and RET fusion tended to have a better OS. Moreover, EGFR MT pts with Adj seemed to have a poorer prognosis than PN pts with Adj.
    Clinical
    |
    EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • RET (Ret Proto-Oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
    |
    KRAS mutation • EGFR mutation • RET fusion • MET exon 14 mutation • ALK fusion • ROS1 fusion • EGFR positive • KRAS exon 4 mutation
    over2years
    Clinicopathologic and Genomic Landscape of Non-Small Cell Lung Cancer Brain Metastases. (PubMed, Oncologist)
    Herein, we defined the clinicopathologic, genomic, and biomarker landscape of a large cohort of patients with NSCLC-BM which can help inform study design of future clinical studies for patients with NSCLC with BM. In certain clinical situations, metastatic NSCLC brain tissue or cerebral spinal fluid specimens may be needed to fully optimize personalized treatment.
    Journal • Tumor Mutational Burden • PD(L)-1 Biomarker • IO biomarker
    |
    EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • MET (MET proto-oncogene, receptor tyrosine kinase) • STK11 (Serine/threonine kinase 11) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • RB1 (RB Transcriptional Corepressor 1) • KEAP1 (Kelch Like ECH Associated Protein 1) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B)
    |
    KRAS mutation • TMB-H • KRAS G12C • MET amplification • MET exon 14 mutation • ALK fusion • ALK mutation • KEAP1 mutation • MET mutation • KRAS G12 • KRAS exon 4 mutation
    |
    Keytruda (pembrolizumab)
    over2years
    S1613, Trastuzumab and Pertuzumab or Cetuximab and Irinotecan Hydrochloride in Treating Patients With Locally Advanced or Metastatic HER2/Neu Amplified Colorectal Cancer That Cannot Be Removed by Surgery (clinicaltrials.gov)
    P2, N=240, Active, not recruiting, Southwest Oncology Group | Recruiting --> Active, not recruiting | N=130 --> 240
    Enrollment closed • Enrollment change
    |
    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog)
    |
    BRAF V600E • HER-2 amplification • BRAF V600 • KRAS exon 4 mutation • BRAF exon 15 mutation
    |
    Herceptin (trastuzumab) • Erbitux (cetuximab) • Perjeta (pertuzumab) • irinotecan • Trazimera (trastuzumab-qyyp)
    over2years
    Driver coexistence characteristics of ALK-fusion in Chinese patients with lung cancer. (ASCO 2022)
    In this cohort, very few of ALK fusion patients coexisted with other driver mutations. Among the co-existence samples, ALK fusion were mainly coexisting with the site mutations of EGFR and KRAS, amplifications of MET and ERBB2, fusions of ROS1 and RET. These samples maybe obtain more effective outcomes by combined or sequential therapies.
    Clinical
    |
    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • RET (Ret Proto-Oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • EML4 (EMAP Like 4) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2)
    |
    KRAS mutation • EGFR mutation • KRAS G12C • BRAF mutation • HER-2 amplification • EGFR L858R • EGFR exon 19 deletion • MET amplification • RET fusion • MET exon 14 mutation • ALK fusion • ALK mutation • RET mutation • ROS1 fusion • MET mutation • KRAS G12 • EGFR G719S • KRAS amplification • NTRK1 mutation • KRAS exon 4 mutation
    |
    Onco PanScan™
    over2years
    A Study to Test Different Doses of BI 1701963 in Combination With Irinotecan in People With Advanced Bowel Cancer With Kirsten Rat Sarcoma Viral Oncogene Homologue (KRAS) Mutation (clinicaltrials.gov)
    P1, N=15, Terminated, Boehringer Ingelheim | N=95 --> 15 | Trial completion date: Feb 2024 --> Apr 2022 | Suspended --> Terminated | Trial primary completion date: Jan 2024 --> Apr 2022; Sponsor decision
    Preclinical • Enrollment change • Trial completion date • Trial termination • Trial primary completion date • Combination therapy
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS mutation • KRAS G12 • KRAS G13 • KRAS exon 2 mutation • KRAS A146 • KRAS Q61 • KRAS A59 • KRAS K117 • KRAS exon 3 mutation • KRAS exon 4 mutation
    |
    irinotecan • BI 1701963
    over2years
    A Study to Find a Safe and Effective Dose of BI 1701963 Alone and in Combination With BI 3011441 in Patients With Advanced Cancer and a Certain Mutation (Kirsten Rat Sarcoma Viral Oncogene Homologue [KRAS]) (clinicaltrials.gov)
    P1, N=8, Terminated, Boehringer Ingelheim | N=124 --> 8 | Trial completion date: Jul 2024 --> Apr 2022 | Suspended --> Terminated | Trial primary completion date: Oct 2023 --> Apr 2022; Sponsor decision
    Preclinical • Enrollment change • Trial completion date • Trial termination • Trial primary completion date • Combination therapy
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS mutation • KRAS G12 • KRAS G13 • KRAS A146 • KRAS Q61 • KRAS A59 • KRAS K117 • KRAS exon 4 mutation
    |
    LNP3794 • BI 1701963
    over2years
    Clinical Implication of KRAS Mutation Variants in Patients With Resected Colon Cancer. (PubMed, Cancer Diagn Progn)
    Although there were no significant differences in survival between patients with exon 2 codon 12 and exon 2 codon 13 mutations, poorer disease-free survival (p=0.085) and overall survival (p=0.005) were seen in those with exon 3 codon 61 mutation than in others. KRAS mutation status was not correlated with survival, but exon 3 codon 61 mutation might be a factor for poor prognosis in patients after resection of CC.
    Journal
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS mutation • MET mutation • KRAS exon 3 mutation • KRAS exon 4 mutation
    over2years
    A Study to Test Different Doses of BI 1701963 in Combination With Irinotecan in People With Advanced Bowel Cancer With Kirsten Rat Sarcoma Viral Oncogene Homologue (KRAS) Mutation (clinicaltrials.gov)
    P1, N=95, Suspended, Boehringer Ingelheim | Recruiting --> Suspended
    Preclinical • Trial suspension • Combination therapy
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS mutation • KRAS G12 • KRAS G13 • KRAS exon 2 mutation • KRAS A146 • KRAS Q61 • KRAS A59 • KRAS K117 • KRAS exon 3 mutation • KRAS exon 4 mutation
    |
    irinotecan • BI 1701963
    over2years
    A Study to Find a Safe and Effective Dose of BI 1701963 Alone and in Combination With BI 3011441 in Patients With Advanced Cancer and a Certain Mutation (Kirsten Rat Sarcoma Viral Oncogene Homologue [KRAS]) (clinicaltrials.gov)
    P1, N=124, Suspended, Boehringer Ingelheim | Recruiting --> Suspended
    Preclinical • Trial suspension • Combination therapy
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS mutation • KRAS G12 • KRAS G13 • KRAS A146 • KRAS Q61 • KRAS A59 • KRAS K117 • KRAS exon 4 mutation
    |
    LNP3794 • BI 1701963
    over2years
    Relationship between perioperative oncological evaluation and recurrence using circulating tumor DNA with KRAS mutation in patients with colorectal cancer. (PubMed, Cancer Med)
    In this study, pathological tumor size, tumor depth, and stage were correlated with preoperative MAF of KRAS, but it was unreliable to predict recurrence by detection of ctDNA with KRAS mutation in the perioperative period of colorectal surgery.
    Journal • Circulating tumor DNA
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS mutation • KRAS G12C • KRAS G12D • KRAS G12V • KRAS G12A • KRAS G12 • KRAS G12S • KRAS Q61H • KRAS A146T • KRAS A146V • KRAS exon 4 mutation
    over2years
    PIER: Induction Therapy With Panitumumab + mFOLFOX-6 in Rectal Cancer and Quadruple Wild-type Mutation Before Surgery (clinicaltrials.gov)
    P2, N=34, Completed, Grupo Espanol Multidisciplinario del Cancer Digestivo | Active, not recruiting --> Completed | Trial completion date: Oct 2022 --> Dec 2021
    Trial completion • Trial completion date • Combination therapy
    |
    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog)
    |
    KRAS exon 3 mutation • KRAS exon 4 mutation • BRAF exon 15 mutation
    |
    5-fluorouracil • Vectibix (panitumumab) • oxaliplatin • leucovorin calcium
    over2years
    Genetic, immunologic and prognostic heterogeneity in CRC patients with KRAS mutations (AACR 2022)
    In addition, different prognosis were found among different mutations of KRAS exon2, in detail, worse PFS was showed in CRC patients with KRAS mutation in exon2 G12D than G12V and G13D. Conclusions CRC patients with KRAS mutations in different exons and different site have different genetic and prognostic characteristics, these patients should be managed differently in clinical practice.
    Clinical • Tumor mutational burden • PD(L)-1 Biomarker • MSi-H Biomarker • IO biomarker
    |
    PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability)
    |
    PD-L1 expression • KRAS mutation • TMB-H • MSI-H/dMMR • KRAS G12C • KRAS G12D • KRAS G12V • KRAS G12 • KRAS G12S • KRAS G13 • KRAS Q61H • KRAS exon 2 mutation • KRAS A146T • KRAS exon 3 mutation • KRAS exon 4 mutation
    |
    PD-L1 IHC 22C3 pharmDx • VENTANA PD-L1 (SP263) Assay
    almost3years
    Clinical implication of KRAS mutation variants in patients with resected colon cancer. (ASCO-GI 2022)
    KRAS mutation status was not correlated with survival, but Exon 3 Codon 61 mutation might be a poor prognostic factor in resected CC patients.
    Clinical
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS mutation • MET mutation • KRAS exon 3 mutation • KRAS exon 4 mutation
    almost3years
    A Study to Test Different Doses of BI 1701963 in Combination With Irinotecan in People With Advanced Bowel Cancer With Kirsten Rat Sarcoma Viral Oncogene Homologue (KRAS) Mutation (clinicaltrials.gov)
    P1, N=95, Recruiting, Boehringer Ingelheim | Trial completion date: Dec 2022 --> Feb 2024 | Trial primary completion date: Oct 2022 --> Jan 2024
    Preclinical • Trial completion date • Trial primary completion date • Combination therapy
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS mutation • KRAS G12 • KRAS G13 • KRAS exon 2 mutation • KRAS A146 • KRAS Q61 • KRAS A59 • KRAS K117 • KRAS exon 3 mutation • KRAS exon 4 mutation
    |
    irinotecan • BI 1701963
    3years
    S1613, Trastuzumab and Pertuzumab or Cetuximab and Irinotecan Hydrochloride in Treating Patients With Locally Advanced or Metastatic HER2/Neu Amplified Colorectal Cancer That Cannot Be Removed by Surgery (clinicaltrials.gov)
    P2, N=130, Recruiting, Southwest Oncology Group | Trial primary completion date: Apr 2022 --> Nov 2022
    Clinical • Trial primary completion date
    |
    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog)
    |
    BRAF V600E • HER-2 amplification • BRAF V600 • KRAS exon 4 mutation • BRAF exon 15 mutation
    |
    Herceptin (trastuzumab) • Erbitux (cetuximab) • Perjeta (pertuzumab) • irinotecan
    over3years
    A Study to Find a Safe and Effective Dose of BI 1701963 Alone and in Combination With BI 3011441 in Patients With Advanced Cancer and a Certain Mutation (Kirsten Rat Sarcoma Viral Oncogene Homologue [KRAS]) (clinicaltrials.gov)
    P1, N=124, Recruiting, Boehringer Ingelheim | Trial completion date: Sep 2023 --> Jul 2024 | Trial primary completion date: Nov 2022 --> Oct 2023
    Clinical • Preclinical • Trial completion date • Trial primary completion date • Combination therapy
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS mutation • KRAS G12 • KRAS G13 • KRAS A146 • KRAS Q61 • KRAS A59 • KRAS K117 • KRAS exon 4 mutation
    |
    LNP3794 • BI 1701963
    over3years
    Prognostic Value of KRAS Exon 3 and Exon 4 Mutations in Colorectal Cancer Patients. (PubMed, J Cancer)
    Among KRAS exon 2 mutated patients, codon 13 mutations predict worse prognosis than codon 12 mutations. Mutations of different KRAS exons should be analyzed separately.
    Clinical • Journal
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS mutation • KRAS exon 2 mutation • KRAS exon 3 mutation • KRAS exon 4 mutation
    over3years
    FOLFOXIRI Plus Panitumumab in Metastatic RAS Wild-type, Left-sided Colorectal Cancer (clinicaltrials.gov)
    P2, N=35, Recruiting, Criterium, Inc. | Trial completion date: Dec 2021 --> Dec 2022 | Trial primary completion date: Sep 2021 --> Sep 2022
    Clinical • Trial completion date • Trial primary completion date
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS exon 2 mutation • KRAS exon 3 mutation • KRAS exon 4 mutation
    |
    5-fluorouracil • Vectibix (panitumumab) • oxaliplatin • irinotecan • leucovorin calcium
    over3years
    STRATEGIC-1: Multi-Line Therapy Trial in Unresectable Metastatic Colorectal Cancer (clinicaltrials.gov)
    P3, N=474, Recruiting, GERCOR - Multidisciplinary Oncology Cooperative Group | Trial completion date: Dec 2019 --> Jun 2021 | Trial primary completion date: Dec 2019 --> Jun 2021
    Clinical • Trial completion date • Trial primary completion date
    |
    KRAS (KRAS proto-oncogene GTPase) • NRAS (Neuroblastoma RAS viral oncogene homolog)
    |
    NRAS mutation • KRAS exon 3 mutation • KRAS exon 4 mutation
    |
    Avastin (bevacizumab) • Erbitux (cetuximab) • 5-fluorouracil • Vectibix (panitumumab) • irinotecan • leucovorin calcium