Colorectal Cancer (CRC) Clinical Trials

About Colorectal Cancer (CRC) trials

CRC trials are organized largely around two axes: RAS pathway status and microsatellite status. RAS testing covers KRAS, NRAS, BRAF, and HRAS. Wild-type patients qualify for anti-EGFR-based trials, KRAS-mutated patients (especially G12C) have their own targeted trial group, and BRAF V600E-mutated patients have a separate dedicated set. Microsatellite status is determined by MMR (mismatch repair) testing, which looks at MLH1, MSH2, MSH6, and PMS2 protein loss, or by MSI testing directly. About 15% of CRC patients have MSI-high or MMR-deficient (dMMR) disease and qualify for immunotherapy trials. HER2 amplification (ERBB2) is tested in a smaller fraction and gates anti-HER2 trials. PD-L1 (CD274) is occasionally relevant. MET and NTRK3 are rare but actionable when present.

Most current CRC trial activity falls into mutation-driven and treatment-line groups. First-line metastatic trials test new combinations on the FOLFOX or FOLFIRI backbone, often with immunotherapy or targeted additions for specific subtypes. Second-line and later trials test ADCs, novel targeted agents, and combinations. MSI-H trials are heavily immunotherapy-focused, both in metastatic and increasingly in early-stage settings (where IO can sometimes replace surgery). KRAS G12C trials are growing as new-generation inhibitors enter the clinic. BRAF V600E trials test targeted combinations. HER2-amplified trials test anti-HER2 combinations and ADCs. MSS (microsatellite stable) IO trials are active right now, trying to find combinations that extend immunotherapy benefit to MSS patients. Rectal-specific trials test total neoadjuvant therapy strategies and watch-and-wait protocols.

Most CRC trials screen on a handful of features beyond mutation status. RAS status (KRAS / NRAS / BRAF / HRAS), where most trials want either confirmed wild-type or confirmed mutant of a specific gene. MMR/MSI status, required for IO trials and excluded for some targeted trials. Sidedness (right vs left colon) matters for some anti-EGFR trials. Prior chemotherapy lines and which regimens (FOLFOX or FOLFIRI, with or without anti-VEGF or anti-EGFR antibodies). Many trials have specific prior-line requirements. Liver metastasis status and resectability for trials that include locoregional treatment. ECOG of 0 or 1 is standard. Adequate organ function, with bilirubin and creatinine cutoffs that vary by trial.

Biomarkers tested in Colorectal Cancer (CRC) trials

These are the molecular markers most commonly required or evaluated in Colorectal Cancer (CRC) eligibility criteria. OncoMatch extracts them from each trial's protocol and matches them against your test results.