High prevalence of NTRK fusions in sporadic dMMR/MSI mCRC RAS/RAF wild-type: an opportunity for a post-immune checkpoint inhibitors progression rescue strategy

Background: Currently, mismatch repair deficient/microsatellite instable (dMMR/MSI) status constitutes a validated predictive marker of response to immune checkpoint inhibitors (ICIs) in patients with metastatic colorectal cancer (mCRC). Unfortunately, some of these patients do not benefit from ICIs. Very limited therapeutic options for patients with dMMR/MSI mCRC after progression on ICI(s) exist. These patients show poor outcomes with conventional chemotherapy. Inhibitors of tropomyosin receptor kinase (TRK) have shown promising activity against neurotrophic tropomyosin receptor kinase (NTRK) fusion-driven cancers. NTRK gene fusions are rare (