Multinational phase 1 trial of SHR-A1811 for heavily pretreated HER2-positive advanced solid tumors

SHR-A1811 (trastuzumab rezetecan) is an antibody-drug conjugate composed trastuzumab, a cleavable linker, and a toposisomerase I inhibitor payload. A multinational phase 1 trial evaluated SHR-A1811 in heavily pretreated HER2-expressing or mutated advanced solid tumors. The trial included 307 patients who had received a median of three (IQR 2-5) previous regimes in the advanced setting. The recommended phase 2 dose was 4.8 or 6.4 mg/kg (for various tumor types) every three weeks. The most common grade 3 or higher adverse events were decreased neutrophil count (38.8%) and decreased leukocyte count (22.8%); with interstitial lung disease in only 2.6%. Serious AEs and deaths occurred in 22.8% and 4.2%, respectively. Objective responses were reported for 59.9% of all patients, 76.3% of patients with HER2-positive breast cancer, 60.4% of patients with HER2-low breast cancer, and 45.9% of patients with nonbreast tumors. The authors conclude that SHR-A1811 exhibited acceptable tolerability and promising antitumor activity in heavily pretreated advanced solid tumors.