426P - Characterization of a novel comprehensive genomic profiling test with better detection of heterozygous deletions and gene fusions

Background

Comprehensive genomic profiling (CGP) is vital for personalized cancer treatment. In Japan, existing healthcare-insurance CGP methods analyze 124-324 genes. ACT Onco+®, an innovative CGP, expands this to 440 DNA genes and 34 RNA genes, providing improved heterozygous deletion detection and RNA-based fusion analysis. This study evaluates ACT Onco+® in advanced solid tumors.

Methods

A cohort of 110 patients, previously examined using conventional CGP, underwent ACT Onco+® analysis.

Results

For Single Nucleotide Variants (SNVs), the initial positive concordance rate of reported alterations was 87.9%, with a 100% predictive value. After examining BAM files, 91.3% of discordance was reconciled, leading to an adjusted concordance rate of 98.9%. Insertions and Deletions (Indels) had a 69.0% concordance rate in initial reported Indels, adjusted to 91.5% after resolving 72.7% discordance. Amplifications and Homozygous Loss had respective positive concordance rates of 76.2% and 66.7%. Heterozygous Deletion was detected in 329 mutations across 61 samples (57.2%) by ACT Onco+®, a result not found in conventional CGP. Fusion Detection with ACT Onco+® revealed three fusions, including one (KIAA1549-BRAF) undetected conventionally. Actionable mutations were reported as 6.80 per sample by ACT Onco+®, compared to 4.87 with conventional CGP.

Conclusions

ACT Onco+® demonstrated higher detection of actionable genetic alterations, emphasizing its enhanced capabilities. Future investigations with larger sample cohorts are necessary to further validate its clinical relevance. This study marks an essential step in advancing personalized cancer therapy, offering more comprehensive insights into genetic variations that may inform treatment strategies.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Tokyo Medical and Dental University.

Funding

ACT med, ACT genomics.

Disclosure

R. Kakuta, S. Ikeda: Financial Interests, Institutional, Research Funding: ACT med, ACT genomics. All other authors have declared no conflicts of interest.