On November 27, 2023 RemeGen Co. Ltd. ("RemeGen" or "the Company") (9995.HK, SHA: 688331), a commercial-stage biotechnology company, reported its two Phase II, open-label, multicenter, single-arm studies for Disitamab Vedotin (RC48-C005 and RC48-C009) have demonstrated consistent efficacy in patients with HER2-positive (immunohistochemistry 3+ or 2+) locally advanced or metastatic urothelial carcinoma (mUC) who have progressed through at least one previous line of systemic chemotherapy (Press release, RemeGen, NOV 27, 2023, View Source [SID1234637980]). The pooled analysis of these two studies have been published in the latest issue of the world-renowned Journal of Clinical Oncology (JCO).

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The pivotal Phase II trial (RC48-C005, NCT03507166) was to evaluate the efficacy and safety of disitamab vedotin in HER2-positive previously treated advanced urothelial carcinoma (UC) patients. Based on the early positive results and the guidance of the National Medical Products Administration (NMPA) in China, the RC48-C005 trial enrollment was prematurely halted, and a subsequent study (RC48-C009, NCT03809013) was conducted to validate the initial findings. A combined analysis of the two studies with adaptive trial design endorsed by the NMPA was required to improve the estimation precision of both efficacy and safety. Both trials demonstrated promising efficacy and manageable safety profiles for patients with metastatic urothelial carcinoma (mUC) who had previously experienced progression on systematic chemotherapy. Based on the robust results from both studies, in January 2022, disitamab vedotin gained conditional approval in China for patients with mUC resistant to platinum-based therapies.

The Company’s CEO, Dr. Jianmin Fang commented, "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 two 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."

Key Results

One hundred and seven patients were enrolled in total and received a 2 mg/kg IV infusion of disitamab vedotin treatment once every two 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. The overall confirmed ORR by BIRC was 50.5% (95% CI, 40.6 to 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 to 10.8). The median PFS and OS were 5.9 months (95% CI, 4.3 to 7.2) and 14.2 months (95% CI, 9.7 to 18.8), respectively. The most common treatment-related adverse events (TRAEs) were peripheral sensory neuropathy (68.2%), leukopenia (50.5%), AST elevation (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%).

Locally advanced or metastatic urothelial carcinoma (UC) has a poor prognosis, with only about 5% of patients at stage IV (metastatic) surviving longer than five years. Platinum-based chemotherapy remains the first-line standard of care for advanced UC with the objective response rates (ORRs) of 44.6%-72% historically and the median overall survival (mOS) of 14.0-15.2 months.

"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 the principal investigator of the studies, Dr. Guo Jun.