Abstract 3544: OncoKB™, MSK’s precision oncology knowledge base: 2023 updates

Abstract

Abstract OncoKBTM is Memorial Sloan Kettering Cancer Center’s (MSK) FDA-recognized precision oncology knowledge base that contains detailed, evidence-based information about the oncogenic effect and therapeutic implications of individual somatic mutations and structural alterations present in patient tumors. Since its public release in 2016, OncoKBTM has expanded to include annotation for >7,500 alterations in ~820 cancer-associated genes. OncoKB supports variant interpretation by the cBioPortal for Cancer Genomics, is used to annotate >15,000 MSK patient sequencing reports annually and its data is publicly available through the website (www.oncokb.org). Programmatic access to OncoKBTM data via its web-based API is freely available to users in an academic setting while users from commercial and hospital settings require a fee-based license. OncoKBTM utilizes its Therapeutic Levels of Evidence system to classify variants based on their tumor type-specific sensitivity or resistance to matched standard care or investigational targeted therapies. To date, OncoKB includes 49 Level 1 genes as well as MSI-H and TMB-H (included in the FDA drug label), 24 Level 2 genes (included in professional guidelines), 35 Level 3A genes (predictive of drug response in well-powered clinical studies), 27 Level 4 genes (predictive of drug response based on compelling biological evidence), and 11 R1/R2 resistance genes. In 2023, OncoKBTM captured the following notable changes in precision oncology drug development: Level 1 annotation of ESR1 ligand-binding domain mutations in breast cancer and promotion from Level 2 to Level 1 of ERBB2 amplification in colorectal cancer following the FDA drug approvals of elacestrant and tucatinib + trastuzumab, respectively. Additionally, KRAS G12C became a Level 2 biomarker in pancreatic and colon cancers with the listing of adagrasib and sotorasib as systemic therapy options for KRAS G12C-mutant disease in the NCCN pancreatic and colon cancer guidelines. IDH1/2 mutations in low grade glioma were annotated as Level 3A based on compelling clinical evidence demonstrating response to the IDH-specific inhibitor vorasidenib. Lastly, noting emerging data with the KRAS G12X-specific inhibitor, RMC-6236, OncoKBTM included all alleles at KRAS position G12 as Level 4. In sum, six novel clinically actionable biomarkers (all Level 1) and 14 follow-on precision oncology therapies for existing leveled biomarkers were added to OncoKBTM in the past year. OncoKBTM’s current focus includes coverage of additional cancer-associated genes, annotation of germline alterations and incorporation of OncoKBTM data into an electronic health record system. Citation Format: Sarah P. Suehnholz, Moriah Nissan, Hongxin Zhang, Ritika Kundra, Calvin Lu, Amanda Dhaneshwar, Nicole Fernandez, Benjamin Preiser, Maria E. Arcila, Marc Ladanyi, Michael F. Berger, Aijazuddin Syed, A. Rose Brannon, Ross Levine, Ahmet Dogan, Alexander Drilon, David B. Solit, Nikolaus Schultz, Debyani Chakravarty. OncoKB™, MSK’s precision oncology knowledge base: 2023 updates [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3544.