A plasma DNA workflow within targeted therapy research

The study evaluated GFH375, an oral inhibitor targeting both active and inactive states of mutant KRAS G12D, in patients with previously treated advanced solid tumors. Alongside safety and antitumor activity assessments, the researchers performed exploratory circulating tumor DNA (ctDNA) analyses to investigate genetic alterations and their potential relationships with treatment outcomes.

Magen’s HiPure Circulating DNA Kit was used at the plasma cfDNA extraction step. The paper identifies the product and catalog number explicitly in its Methods section.

From extracted cfDNA to tumor-associated variant analysis

Following plasma preparation and cfDNA extraction, the researchers quantified the DNA using a Qubit fluorimeter. The extracted cfDNA was then used for library preparation and hybrid capture-based next-generation sequencing with a panel targeting 168 genes in solid tumors.

Baseline ctDNA testing results were available for 27 patients with pancreatic ductal adenocarcinoma, six with non-small cell lung cancer and five with colorectal cancer. These analyses characterized KRAS G12D and co-occurring genetic alterations. Paired baseline and end-of-treatment samples were available for six patients, enabling exploratory assessment of changes in existing variants and newly detected alterations, including changes potentially related to resistance.

The biomarker findings remain exploratory, particularly given the small number of paired samples. The publication nevertheless documents the use of IVD3182 in a plasma cfDNA-to-targeted-NGS workflow within an oncology clinical research study.