Disitamab Vedotin granted FDA breakthrough therapy designation in bladder cancer

September 30, 2020

The antibody-drug conjugate is used for the second-line treatment of patients with HER2-positive locally advanced or metastatic urothelial carcinoma.

The FDA has granted disitamab vedotin (RC48) a breakthrough therapy designation for the treatment of patients with HER2-positive locally advanced or metastatic urothelial carcinoma following treatment with platinum-based chemotherapy, according to RemeGen, the company developing the antibody-drug conjugate (ADC).1

The designation will expedite the development and review of disitamab vedotin in this setting. Phase 2 data presented at the 2019 ASCO Annual Meeting showed that the ADC achieved a confirmed objective response rate of 51.2%, with confirmed responses reported in 22 of 43 patients. The best overall response was a partial response in 26 patients. An additional 13 patients reached stable disease for a disease control rate of 90.7%.2

“An estimated 81,400 new cases of urothelial cancer and 17,980 deaths are predicted in the United States in 2020,i” Jianmin Fang, PhD, founder, CEO, and CSO of RemeGen, stated in a press release. “The high prevalence of metastatic urothelial cancer underscores the need for effective and accessible treatment methods for patients. This breakthrough therapy designation will bring RemeGen one step closer to finding a safe and effective treatment for this devastating disease. We look forward to working with the FDA to advance the clinical development of disitamab vedotin.”

To enroll on the multicenter, open-label,single-arm trial, patients were required to have histologically or cytologically-confirmed diagnosis of inoperable, locally advanced or metastatic urothelial cancer of the bladder, renal pelvis, or ureter; progression or intolerance after at least one systemic chemotherapy for advanced or metastatic disease; a HER2-positive tumor (IHC 2+ or 3+); and an ECOG performance status 0 or 1.

Among the 43 enrolled patients, the median patient age at baseline was 64 years and 76.7% were male. The primary lesion was in the bladder for 51.2% of patients, renal pelvis for 30.2%, and ureter for 25.6%. Overall, 86% of patients had visceral metastases.

Regarding previous treatment, 72.1% (n = 31) of patients had received 1 prior systemic chemotherapy and 27.9% (n = 12) had received ≥2 lines. Eight patients (18.6%) had previously received anti–PD-1/PD-L1 therapy.

The median progression-free survival (PFS) was 6.9 months, with a 6-month PFS rate of 56.9%. The 6- and 12-month overall survival rates were 85.2% and 59.6%, respectively.

Of note, the confirmed objective response rate was 62.5% in patients with prior anti–PD-1/PD-L1 treatment and 56.8% in patients with visceral metastases.

The most frequently occurring treatment-related adverse events (TRAEs) across all grades were hypoesthesia (55.8%), alopecia (55.8%), decreased white blood cell count (55.8%), and decreased neutrophil count (41.9%). The most common grade 3/4 TRAEs were hypoesthesia (16.3%) and decreased neutrophil count (14%). Overall, the most common serious adverse events were intestinal obstruction (4.7%) and incomplete intestinal obstruction (4.7%).


1. RemeGen Announces US FDA Has Granted Breakthrough Therapy Designation for Disitamab Vedotin (RC48) in Urothelial Cancer. Posted online September 25, 2020. Accessed September 30, 2020. https://bit.ly/3n6jbYz.
2. Sheng X, Zhou A-P, Yao X, et al. A phase II study of RC48-ADC in HER2-positive patients with locally advanced or metastatic urothelial carcinoma. J Clin Oncol 37, 2019 (suppl; abstr 4509). doi:10.1200/JCO.2019.37.15_suppl.4509