Dr Grieb on the Need for Novel Biomarkers in CRC

Brian C. Grieb, MD, PhD, instructor, clinical medicine, clinical fellow, Division of Hematology/ Oncology, Department of Medicine, Vanderbilt University Medical Center, discusses remaining unmet needs in the treatment of patients with colorectal cancer (CRC), highlighting the identification of novel pan-CRC biomarkers for drug development.

There has been a multitude of recent advances in the use of targeted therapy in CRC, including both the refinement of newly developed agents and the development of additional tools for patients with specific molecular targets.

For example, the phase 3 SUNLIGHT trial (NCT04737187) investigated the combination of trifluridine/tipiracil (TAS-102; Lonsurf) with bevacizumab (Avastin) in patients with heavily pretreated, refractory metastatic CRC. Previously reported data from the trial showed that the combination improved median overall survival (OS) and progression-free survival (PFS) vs TAS-102 alone.

Additionally, use of the VEGF-targeted agent fruniquinib (HMPL-013) alongside best supportive care (BSC) produced superior OS and PFS benefit vs placebo and BSC in the phase 3 FRESCO-2 trial (NCT04322539). Improved survival outcomes were seen regardless of the number of prior lines of therapy or the specific agent administered. Based on these findings, a new drug application for fruquintinib was granted priority review by the FDA in May of 2023.

Notably, the most recent advances within the treatment space have involved the development of agents targeting well-established biomarkers. Moreover, many of these mutations are only present in smaller patient subsets, signaling a substantial need for research on new actionable biomarkers that are present in many patients with CRC.

Research efforts focused on identifying unconventional targets in CRC, such as the ongoing, open-label, phase 1/2 MYCure trial (NCT04808362), are attempting to address this unmet need. The trial aims to indirectly target WD repeat-containing protein 5 (WDR5), a cofactor for the oncogenic transcription factor MYC, by using the novel small molecule inhibitor Omomyc (OMO-103).

Regardless of whether the findings from MYCure are positive, the identification of more widely applicable biomarkers in CRC is vital to improving outcomes in the overall population, Grieb says.