A new study using the NovellusDx FACT® system was published in Cancer Discovery, adding to the growing body of work utilizing the FACT system to augment NGS data with its in-depth functional significance and its response to drugs.
The work, led by Dr. Scott Kopetz from MD Anderson Cancer Center, presents the results of a phase I study to determine the safety and activity of vemurafenib in combination with irinotecan and cetuximab in patients with refractory, advanced, BRAFV600E-mutated solid tumors. The study found that the combination was well tolerated in patients with refractory, BRAF-mutated mCRC, and both survival outcomes and response rates exceeded prior reports for vemurafenib and for irinotecan plus cetuximab in BRAFV600E mCRC.
Along the study, patients’ cell free-DNA (cfDNA) were analyzed using the Guardant360 test. The progression of mutation and copy number profiles were used to identify several mutations, with unknown function, in the subgroup of patients that developed resistance to the tested drug combination.
“To characterize the functional significance of the found VUS’s, the mutations’ oncogenic activity was measured via the NovellusDx FACT system. Test results showed that indeed these mutations were active, through a common mechanism that confers resistance to the combined treatment.” Said Dr. Gabi Tarcic VP R&D at NovellusDx. “Correct understanding of the functional significance of NGS data can identify drug resistance earlier (before conventional tools), and propose alternative treatment options.”
“We are happy we are able to shed light on the functional significance of these mutations, “said Haim Gil-Ad, NovellusDx’ CEO. “We see more and more that NGS data by itself is insufficient. The NGS needs to be analyzed functionally to gain deeper understanding of the mechanisms and support better physician decisions.”