The following is a summary of “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,” published in the December 2024 issue of Oncology by Zhou et al.  

HER2-targeted antibody-drug conjugates (ADCs) like disitamab vedotin (DV) and trastuzumab deruxtecan (T-Dxd) have shown promise in treating HER2-expressing locally advanced or metastatic urothelial carcinoma (la/mUC), particularly when combined with immunotherapy.  

Researchers conducted a prospective study to evaluate the safety and effectiveness of DV in combination with toripalimab for people with la/mUC.  

This open-label phase 1b/2 study enrolled people with untreated or chemo-refractory la/mUC. In the dose escalation phase, DV was administered at escalating doses of 1.5 and 2.0 mg/kg and toripalimab 3.0 mg/kg every 2 weeks. The primary endpoints were safety and the recommended phase 2 dose (RP2D).  

The results showed that no dose-limiting toxicity was observed. The RP2D was determined to be DV (2.0 mg/kg) + toripalimab (3.0 mg/kg). The confirmed objective response rate (ORR) was 73.2%. The median progression-free survival (PFS) was 9.3 months, and the median OS was 33.1 months. The most common treatment-related adverse events (TRAEs) were increased aspartate aminotransferase (65.9%), increased alanine aminotransferase (63.4%), and peripheral sensory neuropathy (63.4%). Grade 3 or higher TRAEs occurred in 51.2% of people, with gamma-glutamyltransferase increase (12.2%), asthenia (9.8%), and increased alanine aminotransferase (7.3%) being the most common, 1 treatment-related death due to pneumonitis was reported.  

They concluded that the combination of DV and toripalimab showed promising efficacy with a manageable safety profile for people with HER2-unselected la/mUC, supporting the potential as a first-line treatment option.  

Source: annalsofoncology.org/article/S0923-7534(24)04977-9/abstract