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Purpose

To evaluate the efficacy and safety of disitamab vedotin (DV, RC48-ADC), a novel humanized anti–human epidermal growth factor receptor 2 (HER2) antibody conjugated with monomethyl auristatin E, in patients with HER2-positive locally advanced or metastatic urothelial carcinoma (UC) refractory to standard or regular therapies.

Patients and Methods

The data analyzed and reported are from two phase II, open-label, multicenter, single-arm studies (RC48-C005 and RC48-C009) in patients with HER2-positive (immunohistochemistry 3+ or 2+) locally advanced or metastatic UC who have progressed on at least one previous line of systemic chemotherapy. Patients received DV treatment (2 mg/kg IV infusion, once every 2 weeks). The primary end point was objective response rate (ORR) assessed by a blinded independent review committee (BIRC). Progression-free survival (PFS), overall survival (OS), and safety were also assessed.

Results

One hundred and seven patients were enrolled in total. The overall confirmed ORR by BIRC was 50.5% (95% CI 40.6-60.3). Consistent results were observed in prespecified subgroups including patients with liver metastasis and patients previously treated with anti–PD-1/L1 therapies. By the cutoff date of May 10, 2022, the median duration of response was 7.3 months (95% CI 5.7-10.8). The median PFS and OS were 5.9 months (95% CI 4.3-7.2) and 14.2 months (95% CI 9.7-18.8), respectively. The most common treatment-related adverse events (TRAEs) were peripheral sensory neuropathy (68.2%), leukopenia (50.5%), AST increased (42.1%), and neutropenia (42.1%). Fifty-eight (54.2%) patients experienced grade ≥3 TRAEs, including peripheral sensory neuropathy (18.7%) and neutropenia (12.1%).

Conclusion

DV demonstrated a promising efficacy with a manageable safety profile in patients with HER2-positive locally advanced or metastatic UC who had progressed on at least one line of systemic chemotherapy.

Read a Q&A about the study here.