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    BIOMARKER:

    STK11 mutation + TP53 mutation

    i
    Other names: Serine/Threonine-Protein Kinase 11, Liver Kinase B1, Serine/Threonine-Protein Kinase LKB1, Polarization-Related Protein LKB1, STK11, Serine/Threonine Kinase 11, Serine/Threonine-Protein Kinase STK11, Renal Carcinoma Antigen NY-REN-19, TP53, Tumor Protein P53, Cellular Tumor Antigen P53, Phosphoprotein P53, Tumor Protein P53, Antigen NY-CO-13, Transformation-Related Protein 53, Mutant Tumor Protein 53, P53 Tumor Suppressor, Tumor Suppressor P53, Tumor Protein 53, BMFS5, TRP53, BCC7, LFS1
    Entrez ID:
    7157; 6794
    Related biomarkers:
    Expression
    Mutation
    CNA
    Fusion
    Others
    1m
    A Phase II Study of Sotorasib (AMG 510) in Participants with Previously Treated Stage IV or Recurrent KRASG12C Mutated Non-Squamous Non-Small Cell Lung Cancer (ECOG-ACRIN Lung-MAP Sub-Study) (SWOG-Fall 2024)
    Ten additional participants have experienced Grade 4 treatment-related adverse events, nine of which are non-hematologic toxicities. There is one participant with a Grade 3 treatment-related Hepatobil disorders-Other due to autoimmune hepatitis.
    P2 data • IO biomarker • Metastases
    |
    EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • STK11 (Serine/threonine kinase 11) • KEAP1 (Kelch Like ECH Associated Protein 1) • NFE2L2 (Nuclear Factor, Erythroid 2 Like 2) • CYP3A4 (Cytochrome P450, family 3, subfamily A, polypeptide 4)
    |
    TP53 mutation • BRAF V600E • KRAS mutation • EGFR mutation • KRAS G12C • BRAF V600 • EGFR T790M • TP53 wild-type • STK11 mutation • ALK fusion • KEAP1 mutation • ROS1 fusion • KRAS G12 • STK11 mutation + TP53 mutation
    |
    FoundationOne® CDx
    |
    Lumakras (sotorasib)
    8ms
    A Phase II Study of Sotorasib (AMG 510) in Participants with Previously Treated Stage IV or Recurrent KRASG12C Mutated Non-Squamous Non-Small Cell Lung Cancer (ECOG-ACRIN Lung-MAP Sub-Study) (SWOG-Spring 2024)
    There have been two treatment-related deaths, one due to cardiac arrest and one due to pneumonitis. Ten additional participants have experienced Grade 4 treatment-related adverse events, nine of which are non-hematologic toxicities.
    P2 data • IO biomarker • Metastases
    |
    EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • STK11 (Serine/threonine kinase 11) • KEAP1 (Kelch Like ECH Associated Protein 1) • NFE2L2 (Nuclear Factor, Erythroid 2 Like 2) • CYP3A4 (Cytochrome P450, family 3, subfamily A, polypeptide 4)
    |
    TP53 mutation • BRAF V600E • KRAS mutation • EGFR mutation • KRAS G12C • BRAF V600 • EGFR T790M • TP53 wild-type • STK11 mutation • ALK fusion • KEAP1 mutation • ROS1 fusion • KRAS G12 • STK11 mutation + TP53 mutation
    |
    FoundationOne® CDx
    |
    Lumakras (sotorasib)
    1year
    A Phase II Study of Sotorasib (AMG 510) in Participants with Previously Treated Stage IV or Recurrent KRAS G12C Mutated NonSquamous Non-Small Cell Lung Cancer (ECOG-ACRIN LUNG-MAP SUBSTUDY). (SWOG-Fall 2023)
    "Eight additional participants have experienced Grade 4 treatment- related adverse events, seven of which are non- hematologic toxicities. There are two participants with Grade 3 treatment-related Hepatobil disorders-Other due to: autoimmune hepatitis and hepatobiliary disorder."
    P2 data
    |
    EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • STK11 (Serine/threonine kinase 11) • KEAP1 (Kelch Like ECH Associated Protein 1) • NFE2L2 (Nuclear Factor, Erythroid 2 Like 2) • CYP3A4 (Cytochrome P450, family 3, subfamily A, polypeptide 4)
    |
    TP53 mutation • BRAF V600E • KRAS mutation • EGFR mutation • KRAS G12C • BRAF V600 • EGFR T790M • TP53 wild-type • STK11 mutation • ALK fusion • KEAP1 mutation • ROS1 fusion • KRAS G12 • STK11 mutation + TP53 mutation
    |
    FoundationOne® CDx
    |
    Lumakras (sotorasib)
    1year
    A Phase II Study of Sotorasib (AMG 510) in Participants with Previously Treated Stage IV or Recurrent KRAS G12C Mutated NonSquamous Non-Small Cell Lung Cancer (ECOG-ACRIN Lung-MAP SubStudy). (SWOG-Fall 2023)
    Eight additional participants have experienced Grade 4 treatment- related adverse events, seven of which are non- hematologic toxicities. There are two participants with Grade 3 treatment-related Hepatobil disorders-Other due to: autoimmune hepatitis and hepatobiliary disorder.
    P2 data • IO biomarker • Metastases
    |
    EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • STK11 (Serine/threonine kinase 11) • KEAP1 (Kelch Like ECH Associated Protein 1) • NFE2L2 (Nuclear Factor, Erythroid 2 Like 2) • CYP3A4 (Cytochrome P450, family 3, subfamily A, polypeptide 4)
    |
    TP53 mutation • BRAF V600E • KRAS mutation • EGFR mutation • KRAS G12C • BRAF V600 • EGFR T790M • TP53 wild-type • STK11 mutation • ALK fusion • KEAP1 mutation • ROS1 fusion • KRAS G12 • STK11 mutation + TP53 mutation
    |
    FoundationOne® CDx
    |
    Lumakras (sotorasib)
    over1year
    ECOG-ACRIN LUNG-MAP S1900E substudy: A phase II study of sotorasib in participants (Pts) with previously treated stage IV or recurrent KRAS G12C mutant non-squamous (Non-sq) non-small cell lung cancer (NSCLC). (ASCO 2023)
    Two targeted therapeutics, sotorasib and adagrasib, are currently approved for the treatment of previously treated advanced KRAS G12C mutant NSCLC. Sotorasib has also demonstrated superiority to docetaxel in the randomized phase III CodeBreaK 200 study (de Langen et al Lancet...Enrollment started April 2 2021 with conservative accrual targets met, currently with 72% enrolled (84/116) as of Feb 14 2023, including 37, 16, and 31 pts, in cohorts 1, 2, and 3, respectively. Clinical trial information: NCT04625647.
    P2 data • Clinical • Metastases
    |
    KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • STK11 (Serine/threonine kinase 11) • KEAP1 (Kelch Like ECH Associated Protein 1) • NFE2L2 (Nuclear Factor, Erythroid 2 Like 2)
    |
    TP53 mutation • KRAS mutation • KRAS G12C • TP53 wild-type • STK11 mutation • KEAP1 mutation • KRAS G12 • STK11 mutation + TP53 mutation
    |
    FoundationOne® CDx
    |
    docetaxel • Lumakras (sotorasib) • Krazati (adagrasib)
    over2years
    Clinical outcomes and immune phenotypes associated with STK11 co-occurring mutations in non-small cell lung cancer. (PubMed, J Thorac Dis)
    Patients with STK11-mutated NSCLC also demonstrate chemotherapy resistance but have similar outcomes with localized treatment compared to STK11 wild type tumors. Moreover, co-mutations with KRAS or TP53 significantly alter tumor immune landscape of STK11-mutated tumors and therefore response to immunotherapy.
    Clinical data • Journal • Tumor Mutational Burden • PD(L)-1 Biomarker • IO biomarker
    |
    KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • STK11 (Serine/threonine kinase 11) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • KEAP1 (Kelch Like ECH Associated Protein 1) • IFNG (Interferon, gamma)
    |
    TP53 mutation • TMB-H • STK11 mutation • TMB-L • KEAP1 mutation • STK11 mutation + TP53 mutation
    almost4years
    Role of next generation sequencing-based liquid biopsy in advanced non-small cell lung cancer patients treated with immune checkpoint inhibitors: impact of STK11, KRAS and TP53 mutations and co-mutations on outcome. (PubMed, Transl Lung Cancer Res)
    P2; The presence of KRAS/STK11 co-mutation and KRAS/STK11/TP53 co-mutation affected OS only in patients treated with ICIs (HR =10.936, 95% CI: 2.337-51.164, P=0.002; HR =17.609, 95% CI: 3.777-82.089, P<0.001, respectively), indicating a predictive role. Plasma genotyping demonstrated prognostic value of TP53 mutations and predictive value of KRAS/STK11 and KRAS/STK11/TP53 co-mutations.
    Checkpoint inhibition • Journal • Clinical • IO biomarker • Liquid biopsy • Next-generation sequencing
    |
    KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • STK11 (Serine/threonine kinase 11)
    |
    TP53 mutation • KRAS mutation • STK11 mutation • TP53 mutation + KRAS mutation • STK11 mutation + TP53 mutation • KRAS mutation + TP53 mutation
    |
    Guardant360® CDx