Resolution ctDx FIRST plasma assay as a companion diagnostic for adagrasib and its application to longitudinal monitoring.

作者：Ira Pekker, Julia Pollak, Kristy Potts, PuiYee Chan, Chen-Hsun Tsai, Angela Liao, Carly B. Garrison, T Brown, Paul Stull, Daniella Bianchi-Frias, Zhen Li, Christine L. Baker, Kavita Garg · 发表于：Journal of Clinical Oncology · 年份：2022 · DOI：10.1200/jco.2022.40.16_suppl.3057 · 被引用次数：6 · 研究领域：Lung Cancer Treatments and Mutations、Cancer Genomics and Diagnostics、Tuberculosis Research and Epidemiology

3057 Background: KRAS is one of the most commonly mutated oncogenes in cancer. There is a significant need for new treatment options for patients with non–small cell lung cancer (NSCLC) harboring the KRAS G12C mutation. Adagrasib is an investigational, highly selective, oral small molecule inhibitor of KRAS G12C that has demonstrated clinical benefit in patients with KRAS G12C–mutant NSCLC and CRC. Detection of KRAS G12C in cfDNA is minimally invasive and is of benefit to NSCLC patients, many without lesions accessible by tissue biopsy testing. Methods: Resolution ctDx FIRST is a 113 gene comprehensive genomic profiling assay that identifies oncogenic alterations including substitutions, insertions, deletions, gene fusions, and homozygous deletions using targeted NGS sequencing of cfDNA. The Resolution ctDx FIRST assay is being developed as a companion diagnostic for adagrasib in NSCLC patients of the Mirati Study 849-001. Results: The LOD95 for SNVs and indels in KRAS and EGFR at a cfDNA input level of 15ng ranged from 0.34% to 0.82%. No false positives were detected in any samples from healthy donors (N = 60). A total of 230 NSCLC plasma samples were orthogonally tested using a ddPCR assay for KRAS G12C, using 76 plasma samples from Study 849-001 where KRAS G12C positive results had previously been obtained by a tissue assay, and 154 commercially procured NSCLC samples representative of the trial population. The PPA and NPA for Resolution ctDx FIRST plasma testing relative ...