Multicenter phase 2 trial of trastuzumab rezetecan for previously treated, advanced, HER2-mutant non-small cell lung cancer

Trastuzumab rezetecan (aka SHR-A1811) is a novel antibody-drug conjugate consisting of a HER2-directed monoclonal antibody, a cleavable tretrapeptide-based linker, and a DNA topoisomerase I inhibitor. The phase 1-2 HORIZON-Lung trial, at 35 centers in China, evaluated trastuzumab rezetecan in patients with previously treated, locally advanced or metastatic NSCLC with an activating HER2 mutation. Phase 2 results of the trial have now been published. Confirmed objective response by an independent review committee was seen in 69 of 94 patients (ORR 73%; 95% CI 63,3-82,0). The most common grade 3 or 4 treatment-related adverse events weren decreased neutrophil count (40% of patients), decreased white blood cell count (27%), and anemia (23%). Treatment-related serious adverse events occurred in 23% of patients. There were no grade 5 TRAEs. The authors conclude that trastuzumab rezetecan showed clinically meaningful activity and manageable safety in patients with previously treated HER2-mutant NSCLC.