Abstract 6585: OncoKB, MSK’s precision oncology knowledge base

Abstract OncoKB, Memorial Sloan Kettering Cancer Center’s (MSK) precision oncology knowledge base (www.oncokb.org), is an FDA-recognized* somatic variant database that contains information about the oncogenic effect and clinical implications of genomic alterations in cancer. Since its 2016 public release, OncoKB has grown to include annotation for >5,770 alterations in ~700 cancer-associated genes. OncoKB data is integrated into the cBioPortal for Cancer Genomics and used to annotate >12,000 MSK patient sequencing reports annually, encompassing both solid tumor and hematological malignancies. Users in academic, commercial and hospital settings outside MSK can programmatically access OncoKB data via its web API with an OncoKB license, which is free for academic research. To date, users from ~ 1400 institutions across >70 countries have licensed access to OncoKB annotations. The OncoKB Therapeutic (Tx) Levels of Evidence assign tumor-type specific clinical actionability to individual mutational events based on data supporting whether an alteration is predictive of response to matched targeted therapies. To date, OncoKB includes 44 Level 1 genes (included in the FDA drug label), 23 Level 2 genes (included in professional guidelines), 33 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 2022, several major content additions were made to OncoKB based on key shifts in the precision oncology landscape. For example, OncoKB included 2 new tumor-agnostic FDA drug approvals, dabrafenib + trametinib and selpercatinib for BRAF V600E and RET fusion-positive solid tumors respectively (Level 1), capturing 5 tumor-agnostic FDA drug approvals to date. OncoKB promoted ERBB2 oncogenic mutations and FGFR1 fusions to Level 1 following their inclusion as patient eligibility criteria in FDA drug labels for trastuzumab deruxtecan (NSCLC) and pemigatinib (myeloid/lymphoid neoplasms) respectively. NCCN guidelines for uterine sarcoma and pancreatic cancer listed PARP-inhibition for BRCA-mutant disease, making them Level 2 in these indications. Lastly, previously considered undruggable targets, TP53 Y220C and KRAS G12D, were included in OncoKB based on compelling evidence demonstrating response to allele-targeting drugs, PC14586 and RMC-6263, respectively. In sum, 7 novel clinically actionable biomarkers (Levels 1-4) and 11 follow-on precision oncology therapies for existing leveled biomarkers were added to OncoKB in 2022. Current OncoKB efforts are focused on prioritized high-volume cancer gene curation for annotation of whole exome/genome data, annotation of germline alterations and development of a clinical trials matching system. *FDA recognition of OncoKB is partial and limited to the information clearly marked on www.oncokb.org. Citation Format: Sarah P. Suehnholz, Moriah Nissan, Hongxin Zhang, Ritika Kundra, Calvin Lu, Amanda Dhaneshwar, Nicole Fernandez, Stephanie Carrero, Maria E. Arcila, Marc Ladanyi, Michael F. Berger, Aijazuddin Syed, Rose Brannon, Ross Levine, Ahmet Dogan, Ezra Rosen, Alexander Drilon, David B. Solit, Nikolaus Schultz, Debyani Chakravarty. OncoKB, MSK’s precision oncology knowledge base. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6585.