Most recently, the DESTINITY CRC-02 investigated trastuzumab-deruxtecan among patients with HER2-amplified CRC.15 In this study, patients with KRAS-mutant HER2-amplified CRC were enrolled and noted to have a modest response with 5.4 mg/kg dosing with an ORR of 28%, compared to ~40% among patients with RAS wild-type disease.16 Altogether, these studies indicate biomarker selection is key for HER2 targeting in CRC. This evidence concerns the gene KRAS and colorectal carcinoma.