Disitamab vedotin shows promise in HER2+ metastatic urothelial carcinoma

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"In these studies, we were pleased to find that disitamab vedotin has consistent efficacy and manageable safety in patients with chemotherapy-refractory mUC," says Jun Guo, MD.

Combined data from 2 clinical trials (RC48-C005 and RC48-C009) show promising efficacy and safety with disitamab vedotin in patients with HER2-positive (immunohistochemistry 3+ or 2+) locally advanced or metastatic urothelial carcinoma (mUC) whose tumors have progressed following at least 1 previous line of systemic chemotherapy.

The combined ORR across both studies was 50.5%, as confirmed by a blinded independent review committee.

The combined ORR across both studies was 50.5%, as confirmed by a blinded independent review committee.

Pooled results from the studies were published in the Journal of Clinical Oncology.1

"We are firmly committed to providing effective and safe treatment options to prolong and improve the quality of lives of patients with HER2-positive locally advanced or metastatic urothelial cancer. In these studies, we were pleased to find that disitamab vedotin has consistent efficacy and manageable safety in patients with chemotherapy-refractory mUC," said lead author of the studies, Jun Guo, MD, in a news release on the findings.2 Guo is the vice president of clinical oncology at Peking University Cancer Hospital & Institute in Beijing, China.

The initial phase 2 trial (RC48-C005, NCT03507166) of disitamab vedotin sought to assess the safety and efficacy of the treatment in patients with mUC. Based on initial results from the trial, RC48-C005 was prematurely halted following guidance from the National Medical Products Administration (NMPA) in China, and a subsequent phase 2 study (RC48-C009, NCT03809013) was undertaken to validate the results.

According to the news release on the findings, “A combined analysis of the 2 studies with adaptive trial design endorsed by the NMPA was required to improve the estimation precision of both efficacy and safety.”2

In total, 107 patients were enrolled from 17 sites across both studies. Patients received 2 mg/kg intravenous infusion of disitamab vedotin once every 2 weeks. The primary end point was objective response rate (ORR). Secondary end points included duration of response (DoR), progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and safety.

The combined ORR across both studies was 50.5% (95% CI, 40.6 to 60.3), as confirmed by a blinded independent review committee. Of those, 2 (1.9%) patients demonstrated a complete response and 52 (48.6%) demonstrated a partial response. The median DoR was 7.3 months at the time of data cutoff.

Median PFS across the studies was 5.9 months (95% CI, 4.3 to 7.2), with a 12-month PFS rate of 24.7% (95% CI, 16.5 to 33.7). The median OS was 14.2 months (95% CI, 9.7 to 18.8), with an 18-month OS rate of 42.2% (95% CI, 32.5 to 51.5). The DCR was 82.2% (95% CI, 73.7 to 89.0).

Regarding safety, the most common treatment-related adverse events (TRAEs) were peripheral sensory neuropathy in 68.2% of patients, leukopenia in 50.5% of patients, AST increase in 42.1% of patients, and neutropenia in 42.1% of patients. Grade 3 TRAEs were experienced in 58 (54.2%) patients, which included peripheral sensory neuropathy (18.7%) and neutropenia (12.1%). TRAEs led to discontinuation of treatment in 19 patients, 4 of whom experienced grade 2 TRAEs and 15 of whom experienced grade 3 TRAEs. Additionally, 32 patients had a dose reduction due to TRAEs, and 1 went on to discontinue treatment.

Jianmin Fang, PhD, CEO of RemeGen, concluded in the news release, "The reported results demonstrate that disitamab vedotin is among the first HER2-targeted therapies to have meaningful clinical value against metastatic or locally advanced urothelial cancer. These 2 China-based studies have led to the drug's accelerated approval in China and large international studies (NCT04879329, NCT05911295) initiated by our partner, Seagen Inc., are underway."2

References

1. 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. 2023;JCO2202912. doi:10.1200/JCO.22.02912

2. RemeGen announces publication of results from two phase II studies for disitamab vedotin in latest issue of Journal of Clinical Oncology (JCO). News release. RemeGen Co., Ltd. November 27, 2023. Accessed December 7, 2023. https://www.prnewswire.com/news-releases/remegen-announces-publication-of-results-from-two-phase-ii-studies-for-disitamab-vedotin-in-latest-issue-of-journal-of-clinical-oncology-jco-301998515.html

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