DV plus toripalimab shows promise in metastatic urothelial carcinoma

Combination treatment with disitamab vedotin (DV) and toripalimab results in positive objective response rates (ORR) and overall survival (OS), with an acceptable safety profile, in HER2-unselected locally advanced or metastatic urothelial carcinoma (mUC) patients, as shown by the results of a phase Ib/II study.

Forty-one patients with untreated or chemotherapy-refractory locally advanced/mUC were enrolled in this study between August 2020 and December 2021. During the dose-escalation phase, participants received DV at escalating doses of 1.5 and 2.0 mg/kg in combination with toripalimab 3.0 mg/kg once every 2 weeks.

Safety and the recommended phase II dose (R2PD) were the primary endpoints, while ORR, progression-free survival (PFS), and OS were secondary.

Of the patients, six were included in the dose-escalation phase and 35 in the dose-expansion phase. More than half of the participants (61 percent) were treatment-naive. Researchers did not observe dose-limiting toxicity. They determined the R2PD as DV (2.0 mg/kg) plus toripalimab.

By data cutoff (1 March 2024), the confirmed ORR was 73.2 percent, while the median PFS and OS were 9.3 and 33.1 months, respectively.

In terms of safety, elevated aspartate aminotransferase (65.9 percent), increased alanine aminotransferase (63.4 percent), and peripheral sensory neuropathy (63.4 percent) were the most common treatment-related adverse events (TRAEs) observed.

Nearly half (51.2 percent) of the patients experienced grade 3 or higher TRAEs, with increased γ-glutamyltransferase (12.2 percent) being the most common, followed by asthenia (9.8 percent) and elevated alanine aminotransferase (7.3 percent). One patient died, with the cause (ie, pneumonitis) deemed to be related to treatment.