TEST:

Idylla™ ctKRAS Mutation Test

The scalability of Bridge Capture was validated using an expanded panel and synthetic DNA targets, showing a strong linear correlation between observed and expected VAF values. This study demonstrates the scalability and accuracy of the Bridge Capture platform, and its potential to enhance mutation detection and clinical decision-making using ctDNA samples from patients with mCRC.

The LIBImAb Study is a phase III, randomized, openlabel, comparative, multi-center trial to assess the superiority in terms of efficacy of bevacizumab versus cetuximab in combination with FOLFIRI in mCRC pts, RAS/BRAFwt on tumor tissue and RAS/BRAF mutant (RAS/BRAFmut) at liquid biopsy... These data indicate the feasibility of cfDNA-based prospective enrolment in an interventional trial using a test with a rapid TAT for screening of RAS/ BRAF status in plasma. Our preliminary findings also suggest that ctDNA testing might better recapitulate the tumor heterogeneity of mCRC pts thus complementing tissue genomic profiling.

RAS/BRAF mutations have been detected in ctDNA from up to 10% treatment-naive mCRC pts RAS/BRAF wild-type (RAS/BRAFWT) on tissue, while approximately 30% of RAS/BRAFWT pts treated with anti-EGFR agents show RAS/BRAF mutations in ctDNA at progression. LIBImAb is a phase III, randomized, open-label, comparative, multi-centre trial to assess the superiority of bevacizumab versus cetuximab in combination with FOLFIRI in mCRC pts, RAS/BRAFWT on tumor tissue and RAS/BRAF mutant (RAS/BRAFmut) at liquid biopsy... These data show the feasibility of ctDNA-based prospective enrolment in an interventional trial using a test with a rapid TAT for screening RAS/BRAF status in plasma. Our preliminary findings also suggest that ctDNA testing can better recapitulate tumor heterogeneity providing complementary information to tissue genomic profiling.

The primary endpoint is the PFS Plasma samples will be analyzed for KRAS, NRAS, and BRAF mutations by Idylla ctKRAS and Idylla ctNRAS-BRAF-EGFGR. All samples will be also analyzed by NGS, in order to better evaluate the correlation of tumor heterogeneity with pts’ outcomes.

"We tested plasma samples from the Erbitux Metastatic Colorectal Cancer Strategy (ERMES) phase III trial of FOLFIRI+Cetuximab in first-line treatment of RAS/BRAF wild-type mCRC...These data confirm that the occurrence of RAS/BRAF mutations in mCRC patients receiving anti-EGFR agents is relatively frequent. However, the cfDNA dynamics of RAS mutations in patients treated with anti-EGFR agents plus polychemotherapy are complex and might not be directly associated with resistance to treatment."