CAPRI 2 GOIM trial navigates biomarker-driven therapy

The CAPRI 2 GOIM trial demonstrated that liquid biopsy-based comprehensive genomic profiling was feasible and might improve the selection of RAS/BRAF wildtype metastatic colorectal cancer (mCRC) patients for the most appropriate treatments across 3 sequential lines of therapy. The collection of efficacy data is ongoing.

Previous clinical trials have explored the use of cetuximab or panitumumab monoclonal antibodies to target EGFR in the treatment of RAS wildtype mCRC across various treatment lines. Despite significant improvements in patient responses, resistance to anti-EGFR therapy due to innate or acquired mechanisms impairs its effectiveness. Several molecular biomarkers have been identified retrospectively in preclinical and clinical analyses to predict resistance to cetuximab and panitumumab. Among these, RAS mutational status is currently the principal biomarker of poor response to anti-EGFR drugs, and patients with RAS-mutated mCRC are excluded from such treatments.

CAPRI 2 GOIM (NCT05312398) is investigating the efficacy and safety of a biomarker-driven cetuximab-based treatment regimen over 3 treatment lines in mCRC patients with RAS/BRAF wildtype tumours at the start of first-line therapy. The primary endpoint is the response rate for each line of treatment according to the RECIST v1.1 guidelines.

Dr Giulia Martini (University of Campania Luigi Vanvitelli, Italy) presented the initial feasibility analysis of CAPRI 2 GOIM, based on 205 participants in the first-line treatment [1]. Tumour tissue and plasma circulating tumour DNA (ctDNA) next-generation sequencing (NGS) was performed both at the local trial site laboratory as well as centrally through a commercial service, showing a concordance rate of 90.7% (186/205). Baseline ctDNA plasma analysis identified additional molecular alterations compared with PCR-based tumour tissue analyses, which could be involved in resistance to anti-EGFR drugs in mCRC. There was a high concordance between tumour tissue and ctDNA NGS analysis (95.1%; 156/165) at both local and centralised laboratories.

Dr Martini concluded that using local laboratories for liquid biopsy-based comprehensive genomic profiling was feasible. Furthermore, efforts to improve sensitivity are ongoing and include: tracking more mutations (whole-exome sequencing versus panel), reducing background noise (sequencing peripheral blood mononuclear cells, technical improvements), and increasing circulating free DNA input.

1. Martini G, et al. Evaluation of plasma assessed comprehensive genomic profiling before first-line treatment with FOLFIRI plus cetuximab in RAS/BRAFV600E wild type metastatic colorectal cancer patients in the CAPRI 2-GOIM trial. Abstract 6MO, ESMO Gastrointestinal Cancers Congress 2024, 26–29 June, Munich, Germany.

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Posted on 21 August 2024