trastuzumab + irinotecan

**Trastuzumab + irinotecan** is a combination regimen consisting of trastuzumab, a humanized monoclonal antibody that binds to the extracellular domain of HER2 to inhibit signaling and mediate antibody-dependent cellular cytotoxicity, paired with irinotecan, a topoisomerase I inhibitor that stabilizes the enzyme-DNA complex to induce DNA damage and apoptosis. Evaluated in a phase II trial (NCT03185988) for pretreated HER2-positive, KRAS/BRAF wild-type metastatic colorectal cancer (mCRC), it demonstrated an objective response rate of 33.3%, median progression-free survival of 4.3 months, and acceptable tolerability with mostly grade 1-2 adverse events like diarrhea, nausea, and leukopenia. High HER2 copy number correlated with better responses, while MAPK pathway alterations drove resistance.[1][2][3]