Abstract 691: Decentralized pan-cancer tumor profiling: a comprehensive performance evaluation of the MSK-IMPACT® Assay with SOPHiA DDMTM
Authors: Julien Pontis, Fuad Mohammad, Anjali Anjali, Yvan Wenger, Florian Klemm, Anita F. Bowman, Brian Houck-Loomis, Jacklyn Casanova-Murphy, A. Rose Brannon, Micheal F. Berger, Zhenyu Xu
Journal: Cancer Research (2025)

Abstract Background: Molecular profiling of solid tumors through FFPE (Formalin-Fixed Paraffin-Embedded) tissue samples is crucial for personalized cancer treatment. MSK-IMPACT® (Memorial Sloan Kettering - Integrated Mutation Profiling of Actionable Cancer Targets) is a well-established, high-throughput genomic assay designed to identify known cancer-driving alterations in solid tumors from FFPE tissue samples. SOPHiA GENETICS is developing a decentralized version of this assay, integrating key features of MSK-IMPACT® including comprehensive genomic profiling, the utilization of hybrid capture-based next-generation sequencing, and the identification of actionable somatic mutations. This report presents the results from a performance evaluation study conducted during the development of this product. Methods: A cohort of 167 FFPE solid tumor samples and matched normal tissue were collected from cancer patients and processed at MSKCC (Memorial Sloan Kettering Cancer Center) according to the validated standard operating procedures for MSK-IMPACT®, which involves DNA extraction, library preparation, hybrid capture targeting 505 actionable cancer genes, and sequencing on an Illumina platform. In parallel, SOPHiA GENETICS processed the same samples using proprietary enrichment techniques, and sequencing was performed on Illumina platforms. Somatic variants were identified using a robust bioinformatics pipeline, and the results were compared with those obtained by MSKCC to assess the accuracy of the decentralized “MSK-IMPACT® powered with SOPHiA DDM™” solution. Results: A total of 1736 somatic mutations were detected, with variant allele fractions (VAF) as low as 1.1% and a median of 5 variants with coding impact per sample. The positive percent agreement (PPA) for all detected variants with the original MSK-IMPACT® assay is 99.3% for SNV/INDEL with a PPA &amp;gt;98% down to 2.5-6% VAF. Furthermore, PPA for CNVs is 94.6%, and overall percent agreement for MSI and TMB of 99.4% and 98.8%, respectively. Conclusions: The findings affirm that the decentralized “MSK-IMPACT® powered with SOPHiA DDM™” solution delivers a high level of concordance with the established results by MSK-IMPACT®. Future studies are planned to further verify the analytical and clinical performance and to evaluate the utility in routine clinical practice. This solution equips laboratories with a premier, comprehensive testing capability that identifies SNV/INDEL, CNV, DNA fusion, and the critical immuno-oncology biomarkers TMB and MSI. Citation Format: Julien Pontis, Fuad Mohammad, Anjali Anjali, Yvan Wenger, Florian Klemm, Anita F. Bowman, Brian Houck-Loomis, Jacklyn Casanova-Murphy, A. Rose Brannon, Micheal F. Berger, Zhenyu Xu. Decentralized pan-cancer tumor profiling: a comprehensive performance evaluation of the MSK-IMPACT Assay with SOPHiA DDM [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 691.