OncoKB New Data Release - July 28, 2025
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Data Release v5.0
July 28, 2025
What's New
Release of OncoKB™ SOP v5.1
Update to OncoKB’s gene classification system to include a new category, “Insufficient Evidence,” for genes with weak or conflicting evidence describing their role as oncogenes or tumor suppressor genes. For more details, please refer to the OncoKB™ SOP v5.1.
Updated Therapeutic Implications:
New alteration(s) with a tumor type-specific level of evidence
Level 1: EGFR Oncogenic Mutations (excluding L858R, Exon 19 deletions, T790M, G719, L861Q, S768I, Exon 20 in-frame insertions, G724S, L718Q/V, D761Y, Exon 19 in-frame insertions, L747P and Kinase Domain Duplication, which are already leveled) in non-small cell lung cancer based on FDA approval of datopotamab deruxtecan for adults with locally advanced or metastatic EGFR-mutated non-small cell lung cancer (PMID: 39761483, 39250535)
Promotion of tumor type-specific level of evidence for an alteration
Level 1: EGFR G724S and L718Q/V in non-small cell lung cancer promoted from Level 3A to Level 1 based on FDA approval of datopotamab deruxtecan for adults with locally advanced or metastatic EGFR-mutated non-small cell lung cancer (PMID: 39761483, 39250535)
Level 3A sensitivity-associated evidence currently in OncoKB™ for EGFR G724S and L718Q/V in non-small cell lung cancer: Afatinib
Level 1: EGFR Exon 19 in-frame insertions in non-small cell lung cancer promoted from Level 3A to Level 1 based on FDA approval of datopotamab deruxtecan for adults with locally advanced or metastatic EGFR-mutated non-small cell lung cancer (PMID: 39761483, 39250535)
Level 3A sensitivity-associated evidence currently in OncoKB™ for EGFR Exon 19 in-frame insertions in non-small cell lung cancer: Erlotinib, Gefitinib, Patritumab Deruxtecan
Level 1: EGFR Kinase Domain Duplication in non-small cell lung cancer promoted from Level 3A to Level 1 based on FDA approval of datopotamab deruxtecan for adults with locally advanced or metastatic EGFR-mutated non-small cell lung cancer (PMID: 39761483, 39250535)
Level 3A sensitivity-associated evidence currently in OncoKB™ for EGFR Kinase Domain Duplication in non-small cell lung cancer: Afatinib, Erlotinib
Level 1: EGFR L747P in non-small cell lung cancer promoted from Level 4 to Level 1 based on FDA approval of datopotamab deruxtecan for adults with locally advanced or metastatic EGFR-mutated non-small cell lung cancer (PMID: 39761483, 39250535)
Level 4 sensitivity-associated evidence currently in OncoKB™ for EGFR L747P in non-small cell lung cancer: Afatinib
Level 1: EGFR D761Y in non-small cell lung cancer promoted from Level 4 to Level 1 based on FDA approval of datopotamab deruxtecan for adults with locally advanced or metastatic EGFR-mutated non-small cell lung cancer (PMID: 39761483, 39250535)
Level 4 sensitivity-associated evidence currently in OncoKB™ for EGFR D761Y in non-small cell lung cancer: Osimertinib
Addition of drug(s) associated with a tumor type-specific leveled alteration(s) currently in OncoKB™ (without changing the alteration's highest level of evidence)
Level 1: Addition of Datopotamab Deruxtecan and Sunovertinib to EGFR Exon 20 in-frame insertions in non-small cell lung cancer based on FDA approval of datopotamab deruxtecan for adults with locally advanced or metastatic EGFR-mutated non-small cell lung cancer (PMID: 39761483, 39250535) and FDA approval of sunovertinib for adult patients with locally advanced or metastatic non-small cell lung cancer with EGFR exon 20 in-frame insertions (Abstract: Yang, JCH. et al., ASCO 2024)
Level 1 sensitivity-associated therapeutics currently in OncoKB™ for EGFR Exon 20 in-frame insertions in non-small cell lung cancer: Amivantamab, Amivantamab + Chemotherapy
Level 1: Addition of Datopotamab Deruxtecan to EGFR Exon 19 in-frame deletions and L858R in non-small cell lung cancer based on FDA approval of datopotamab deruxtecan for adults with locally advanced or metastatic EGFR-mutated non-small cell lung cancer (PMID: 39761483, 39250535)
Level 1 sensitivity-associated therapeutics currently in OncoKB™ for EGFR Exon 19 in-frame deletions and L858R in non-small cell lung cancer: Amivantamab + Chemo, Erlotinib, Gefitinib, Dacomitinib, Afatinib, Osimertinib, Lazertinib + Amivantamab, Erlotinib + Ramucirumab, Osimertinib + Chemotherapy
Level 1: Addition of Datopotamab Deruxtecan to EGFR G719, L861Q and S768I in non-small cell lung cancer based on FDA approval of datopotamab deruxtecan for adults with locally advanced or metastatic EGFR-mutated non-small cell lung cancer (PMID: 39761483, 39250535)
Level 1 sensitivity-associated therapeutics currently in OncoKB™ for EGFR G719, L861Q and S768I in non-small cell lung cancer: Afatinib
Level 1: Addition of Datopotamab Deruxtecan to EGFR T790M in non-small cell lung cancer based on FDA approval of datopotamab deruxtecan for adults with locally advanced or metastatic EGFR-mutated non-small cell lung cancer (PMID: 39761483, 39250535)
Level 1 sensitivity-associated therapeutics currently in OncoKB™ for EGFR T790M in non-small cell lung cancer: Osimertinib
Gene Curation:
Addition of 2 new genes:
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