The combination of disitamab vedotin plus toripalimab-tpzi (Loqtorzi) has demonstrated encouraging efficacy with a manageable safety profile in patients with locally advanced or metastatic urothelial carcinoma (la/mUC), according to long-term data from a phase 1b/2 clinical trial (NCT04264936; RC48-C014) published in Annals of Oncology. The trial's initial data were presented at the 2023 American Society of Clinical Oncology Annual Meeting in Chicago, Illinois.
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Trial Design and Dosage: The trial was conducted as a dose-escalation/dose-expansion study. In phase 1, patients received disitamab vedotin at dose levels of 1.5 mg/kg and 2.0 mg/kg in combination with 3.0 mg/kg toripalimab once every 2 weeks. No dose-limiting toxicities were observed, leading to the determination of the recommended phase 2 dose (RP2D) as 2.0 mg/kg disitamab vedotin plus 3.0 mg/kg toripalimab.
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Efficacy Outcomes: At a median follow-up of 33.2 months, the confirmed objective response rate (ORR) was 73.2%, with 4 complete responses and 26 partial responses. The disease control rate was 90.2%, and the median progression-free survival (PFS) was 9.3 months. The median overall survival (OS) was 33.1 months, with an OS rate of 49.2% at 36 months.
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Safety Profile: All patients experienced a treatment-related adverse event (TRAE), with the most common being an increase in aspartate aminotransferase (65.9%), alanine aminotransferase (63.4%), and peripheral sensory neuropathy (63.4%). TRAEs of grade 3 or higher were reported in 51.2% of patients, with one treatment-related death due to pneumonitis.
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Patient Demographics and Treatment Duration: The trial enrolled 41 patients with la/mUC, with a median age of 66 years. Patients received treatment for a median duration of 8.0 months.
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Future Studies: Two randomized phase 3 trials of disitamab vedotin plus toripalimab are currently underway, with primary completion expected in 2026.
This combination represents a promising first-line option for la/mUC, offering hope for improved treatment outcomes in this challenging disease.
