Disitamab Vedotin Shows Promise Among Patients With HER2-Positive Urothelial Carcinoma

According to an analysis of the data from 2 phase 2, open-label, multi-center, single-arm studies, disitamab vedotin showed promising efficacy with a tolerable safety profile among patients with HER2-positive locally advanced or metastatic urothelial carcinoma who had progressed on at least 1 line of systemic chemotherapy.

“Disitamab vedotin is a novel humanized anti-human epidermal growth factor receptor 2 (HER2) antibody conjugated with monomethyl auristatin E,” wrote Xinan Sheng, MD, Peking University Cancer Hospital & Institute, Beijing, China and coauthors, noting that 2 phase 2 studies in China “showed promising efficacy and manageable safety in patients with [metastatic urothelial carcinoma] who had progressed on previous systemic chemotherapy.” Based on the results from 1 of those studies (RC48-C009) disitamab vedotin was approved for patients platinum-refractory patients with metastatic urothelial carcinoma in China in January of 2022.

The 2 studies analyzed were RC48-C005 and RC48-C009, both phase 2, open-label, multicenter, single-arm trials. Between the 2 studies, 107 patients with HER2-positive locally advanced or metastatic urothelial carcinaom who have progressed on ≥1 previous line of systemic chemotherapy. Patients received 2 mg/kg of disitamab vedotin once every 2 weeks. The primary end point was objective response rate (ORR) as assessed by a blinded independent review committee. Other end points included progression-free survival (PFS), overall survival (OS), and safety.

The overall ORR was 50.5%, with a similar response across prespecified subgroups, including patients with liver metastases and those previously treated with anti-PD-1/L1 therapies. The median duration of response was 7.3 months. The median PFS and OS were 5.9 months and 14.2 months, respectively. The most common treatment-related adverse events were peripheral sensory neuropathy, leukopenia, AST increase, and neutropenia. The rate of grade ≥3 treatment-related adverse events was 54.2%, including peripheral sensory neuropathy and neutropenia.

Dr Sheng et al, concluded, “[Disitamab vedotin] demonstrated a promising efficacy with a manageable safety profile in patients with HER2-positive locally advanced or metastatic [urothelial carcinoma] who had progressed on at least 1 line of systemic chemotherapy.”

Associate editor for Journal of Clinical Oncology, Michael A Carducci, MD, Johns Hopkins University, Baltimore, Maryland, added, “This report is among the first HER2 directed therapies for metastatic or locally advanced urothelial carcinoma to demonstrate meaningful clinical activity. These 2 China based studies have led to approval there and are being evaluated in large international studies.”

Source:

Sheng X, Wang L, He Z, et al. Efficacy and safety of disitamab vedotin in patients with human epidermal growth factor receptor 2-positive locally advanced or metastatic urothelial carcinoma: A combined analysis of two phase II clinical trials. J Clin Oncol. Published online November 21, 2023. doi:10.1200/JCO.22.02912