Disitamab Vedotin plus Toripalimab in HER2-Expressing Advanced Urothelial Cancer

Area of Science:

• Oncology
• Immunotherapy
• Urothelial Carcinoma

Background:

• HER2-targeted antibody-drug conjugate monotherapy shows promise in advanced urothelial cancer.
• Disitamab vedotin (an HER2-specific ADC) combined with PD-1 immunotherapy demonstrates antitumor activity and safety.

Purpose of the Study:

• To evaluate the efficacy and safety of disitamab vedotin plus toripalimab versus chemotherapy in untreated HER2-expressing locally advanced or metastatic urothelial cancer.

Main Methods:

• Phase 3, multicenter, open-label, randomized trial.
• 484 patients randomized 1:1 to disitamab vedotin + toripalimab (2-weekly) or chemotherapy (3-weekly).
• Dual primary endpoints: progression-free survival (PFS) and overall survival (OS).

Main Results:

• Disitamab vedotin + toripalimab significantly improved PFS (13.1 vs. 6.5 months; HR 0.36) and OS (31.5 vs. 16.9 months; HR 0.54).
• Objective response rate was higher with disitamab vedotin + toripalimab (76.1% vs. 50.2%).
• Disitamab vedotin + toripalimab showed a more favorable safety profile with fewer grade 3+ adverse events (55.1% vs. 86.9%).

Conclusions:

• Disitamab vedotin plus toripalimab offers superior outcomes compared to chemotherapy for untreated HER2-expressing advanced urothelial cancer.
• This combination represents a promising new treatment strategy for this patient population.