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    BIOMARKER:

    EGFR S492R

    i
    Other names: EGFR, ERBB, ERBB1, Epidermal growth factor receptor
    Entrez ID:
    1956
    Related biomarkers:
    Expression
    Mutation
    CNA
    Fusion
    Others
    11ms
    Panitumumab With or Without Trametinib in Treating Patients With Stage IV Colorectal Cancer (clinicaltrials.gov)
    P2, N=59, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Jan 2024 --> Jan 2025 | Trial primary completion date: Jan 2024 --> Jan 2025
    Trial completion date • Trial primary completion date • Combination therapy • Metastases
    |
    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog) • MAP2K1 (Mitogen-activated protein kinase kinase 1)
    |
    KRAS mutation • BRAF mutation • NRAS mutation • KRAS wild-type • RAS wild-type • NRAS wild-type • KRAS exon 2 mutation • EGFR S492R • KRAS exon 2 wild-type
    |
    Mekinist (trametinib) • Vectibix (panitumumab)
    over1year
    Panitumumab With or Without Trametinib in Treating Patients With Stage IV Colorectal Cancer (clinicaltrials.gov)
    P2, N=59, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Jul 2024 --> Jan 2024 | Trial primary completion date: Jul 2024 --> Jan 2024
    Trial completion date • Trial primary completion date • Combination therapy • Metastases
    |
    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog) • MAP2K1 (Mitogen-activated protein kinase kinase 1)
    |
    KRAS mutation • BRAF mutation • NRAS mutation • KRAS wild-type • RAS wild-type • NRAS wild-type • KRAS exon 2 mutation • EGFR S492R • KRAS exon 2 wild-type
    |
    Mekinist (trametinib) • Vectibix (panitumumab)
    over1year
    Panitumumab With or Without Trametinib in Treating Patients With Stage IV Colorectal Cancer (clinicaltrials.gov)
    P2, N=59, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting | Trial primary completion date: Jul 2023 --> Jul 2024
    Enrollment closed • Trial primary completion date • Combination therapy • Metastases
    |
    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog) • MAP2K1 (Mitogen-activated protein kinase kinase 1)
    |
    KRAS mutation • BRAF mutation • NRAS mutation • KRAS wild-type • RAS wild-type • NRAS wild-type • KRAS exon 2 mutation • EGFR S492R • KRAS exon 2 wild-type
    |
    Mekinist (trametinib) • Vectibix (panitumumab)
    almost2years
    Panitumumab plus trifluridine/tipiracil as third-line anti-EGFR rechallenge therapy in chemo-refractory RAS WT metastatic colorectal cancer: The VELO randomized phase II clinical trial. (ASCO-GI 2023)
    P2 | "This is the first prospective randomized trial which evaluated anti-EGFR monoclonal antibody (panitumumab) in addition to standard of care (trifluridine-tipiracil) as third-line rechallenge therapy in chemo-refractory RASWT mCRC patients. Baseline liquid biopsy allows selection of RAS/BRAF WT ctDNA patients who could have a relevant clinical benefit. Clinical trial information: NCT05468892."
    P2 data • Clinical
    |
    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog)
    |
    BRAF V600E • KRAS mutation • NRAS mutation • BRAF V600 • BRAF wild-type • RAS wild-type • EGFR S492R
    |
    FoundationOne® Liquid CDx • Idylla™ BRAF Mutation Test • Idylla™ KRAS Mutation Test
    |
    Vectibix (panitumumab) • Lonsurf (trifluridine/tipiracil)
    2years
    Idylla BRAF and NRAS (AMP 2022)
    "The 23 common mutations detected in the BRAF and NRAS genes using this assay have significant impact on therapeutic selection. Somatic variants in the BRAF gene have been found in 37%-50% of all malignant melanomas, whereas somatic variants in the NRAS gene are found in 13%-25% of all melanomas. The Biocartis Idylla system offers a simple and rapid method to obtain somatic mutation information in these two genes that are of clinical importance."
    EGFR (Epidermal growth factor receptor) • BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog)
    |
    EGFR mutation • NRAS mutation • BRAF V600 • NRAS Q61K • NRAS Q61 • NRAS Q61R • NRAS G13 • NRAS Q61L • EGFR S492R
    |
    Idylla™ BRAF Mutation Test • Idylla™ EGFR Mutation Test • Idylla™ NRAS-BRAF-EGFR S492R Mutation Assay
    over2years
    Structure-guided and phage-assisted evolution of a therapeutic anti-EGFR antibody to reverse acquired resistance. (PubMed, Nat Commun)
    The evolved cetuximab variants (Ctx-VY, Ctx-Y104D and Ctx-W52D) with one or two amino acid substitutions in the complementarity-determining region inherit the optimized physical and chemical properties of cetuximab to a great extent, thus ensuring their druggability. Our data collectively show that structure-guided and phage-assisted evolution is an efficient and general approach for reversing receptor mutation-mediated resistance to therapeutic antibody drugs.
    Preclinical • Journal
    |
    EGFR (Epidermal growth factor receptor)
    |
    EGFR S492R • EGFR G465R
    |
    Erbitux (cetuximab)
    over2years
    Panitumumab With or Without Trametinib in Treating Patients With Stage IV Colorectal Cancer (clinicaltrials.gov)
    P2, N=84, Recruiting, M.D. Anderson Cancer Center | Unknown status --> Recruiting | Trial completion date: Dec 2021 --> Jul 2024 | Trial primary completion date: Dec 2021 --> Jul 2023
    Enrollment open • Trial completion date • Trial primary completion date • Combination therapy
    |
    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog) • MAP2K1 (Mitogen-activated protein kinase kinase 1)
    |
    KRAS mutation • BRAF mutation • NRAS mutation • KRAS wild-type • RAS wild-type • NRAS wild-type • KRAS exon 2 mutation • EGFR S492R • KRAS exon 2 wild-type
    |
    Mekinist (trametinib) • Vectibix (panitumumab)
    over3years
    Cetuximab Rechallenge Plus Avelumab in Pretreated Patients With RAS Wild-type Metastatic Colorectal Cancer: The Phase 2 Single-Arm Clinical CAVE Trial. (PubMed, JAMA Oncol)
    Plasma ctDNA analysis before treatment may allow selection of patients who could benefit. ClinicalTrials.gov Identifier: NCT04561336.
    Clinical • P2 data • Journal • MSi-H Biomarker • PD(L)-1 Biomarker
    |
    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog) • MSI (Microsatellite instability)
    |
    MSI-H/dMMR • BRAF mutation • EGFR S492R
    |
    Erbitux (cetuximab) • Bavencio (avelumab)
    4years
    Frequency of S492R mutations in the epidermal growth factor receptor: analysis of plasma DNA from patients with metastatic colorectal cancer treated with panitumumab or cetuximab monotherapy. (PubMed, Cancer Biol Ther)
    These results may support targeting treatment to small patient subgroups based on the presence of emerging EGFR mutations and provide a molecular rationale for rechallenging with a different anti-EGFR agent in patients who develop resistance. Prospective studies are needed to evaluate the efficacy of panitumumab in the EGFR p.S492R mutant population.
    Clinical • Journal
    |
    EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase)
    |
    EGFR mutation • KRAS exon 2 mutation • EGFR S492R
    |
    Erbitux (cetuximab) • Vectibix (panitumumab)
    4years
    Emerging RAS, BRAF, and EGFR mutations in cell-free DNA of metastatic colorectal patients are associated with both primary and secondary resistance to first-line anti-EGFR therapy. (PubMed, Int J Clin Oncol)
    Emerging RAS, BRAF, and EGFR mutations occurred in patients with primary and secondary resistance to EGFR blockade. The detection of these mutations in cfDNA is a promising approach to predict treatment response and secondary resistance.
    Clinical • Journal
    |
    EGFR (Epidermal growth factor receptor) • BRAF (B-raf proto-oncogene)
    |
    EGFR mutation • BRAF mutation • EGFR S492R