Multicenter phase 3 trial of disitamab vedotin plus toripalimab in HER2-expressing advanced urothelial cancer

The multicenter phase 3 RC48-C016 trial in China randomized patients with previously untreated HER2-expressing locally advanced or metastatic urothelial cancer 1:1 to the HER2-directed antibody-drug conjugate disitimab vedotin plus toripalimab (anti-PD-1) or chemotherapy (gemcitabine plus cisplatin or carboplatin). Coprimary endpoints were progression-free survival and overall survival. For both endpoints, disitimab vedotin plus toripalimab was significantly superior to chemotherapy. The safety profile of disitamab vedotin plus toripalimab was more favorable than that of chemotherapy, with grade 3 or higher treatment-related adverse events reported for 55.1% of patients in the disitimab vedotin plus toripalimab group and 86.9% of patients in the chemotherapy group. The authors conclude that the combination of disitamab vedotin and toripalimab led to significantly longer PFS and OS than chemotherapy among patients with untreated HER2-expressing locally advanced or metastatic urothelial cancer.