Optimal Disitamab Vedotin Dose for Patients With Chemotherapy-Refractory Advanced Urothelial Carcinoma
According to results from the phase 1b/2 RC48-C014 study, the addition of 2 mg/kg of disitamab vedotin, a human epidermal growth factor receptor 2 (HER2)-targeted antibody-drug conjugate (ADC), to toripalimab is preferable to 1.5 mg/kg among patients with chemotherapy-refractory locally advanced or metastatic urothelial carcinoma.
In this open-label study, researchers enrolled 41 patients (dose-escalation n = 6; dose-expansion n = 35) with chemotherapy-refractory locally advanced or metastatic urothelial carcinoma to receive either 1.5 mg/kg or 2 mg/kg of disitamab vedotin plus 3 mg/kg of toripalimab, once every 2 weeks. The primary end point was recommended phase 2 dose. Key secondary end points included objective response rate (ORR), progression-free survival (PFS), and overall survival (OS).
At analysis, no dose-limiting toxicities were observed and 2 mg/kg of disitamab vedotin was identified as the recommended phase 2 dose. The confirmed ORR was 73.2%. The median PFS was 9.3 months, and the median OS was 33.1 months. The most common treatment-related adverse events included aspartate aminotransferase increase (65.9%), alanine aminotransferase increase (63.4%), and peripheral sensory neuropathy (63.4%). The most common grade ≥3 treatment-related adverse events included gamma-glutamyltransferase increase (12.2%), asthenia (9.8%), and alanine aminotransferase increase (7.3%). One treatment-related death occurred.
“This combination represents a promising first-line option for [locally advanced or metastatic urothelial carcinoma],” concluded study authors. They added there is currently an ongoing randomized phase 3 study to investigate this regimen.
Source:
Zhou L, Yang KW, Zhang S, et al. Disitamab vedotin plus toripalimab in patients with locally advanced or metastatic urothelial carcinoma (RC48-C014): A phase 1b/2 dose-escalation and dose-expansion study. Ann Oncol. Published online: December 9, 2024. doi: 10.1016/j.annonc.2024.12.002
