Open-label, Multicenter, Phase II Study of RC48-ADC, a HER2-Targeting Antibody-Drug Conjugate, in Patients with Locally Advanced or Metastatic Urothelial Carcinoma

Cancer shared this article with you from Inoreader Open-label, Multicenter, Phase II Study of RC48-ADC, a HER2-Targeting Antibody-Drug Conjugate, in Patients with Locally Advanced or Metastatic Urothelial Carcinoma Via Clinical Cancer Research recent ... Purpose: To evaluate the efficacy and safety of RC48-ADC, a novel humanized anti-HER2 antibody conjugated with monomethyl auristatin E, in patients with HER2+ locally advanced or metastatic urothelial carcinoma (mUC) refractory to standard therapies. Patients and Methods: This was a phase II, open-label, multicenter, single-arm study of patients with HER2+ (IHC status 3+ or 2+) locally advanced or mUC who previously failed at least one line of systemic chemotherapy. The primary endpoint was the objective response rate (ORR) assessed by a blinded independent review committee (BIRC). The secondary endpoint included progression-free survival (PFS), disease control rate, duration of response, overall survival (OS), and safety. Results: Forty-three patients were enrolled. The median follow-up was 20.3 months. The overall confirmed ORR as assessed by the BIRC was 51.2% [95% confidence interval (CI), 35.5%–66.7%]. Similar responses were observed in prespecified subgroups, such as those with liver metastasis and those previously treated with anti–programmed cell death 1 (PD-1)/programmed death ligand 1 (PD-L1) therapies. The median PFS and OS were 6.9 months (95% CI, 5.6–8.9) and 13.9 months (95% CI, 9.1–NE), respectively. The most common treatment-related adverse events (TRAE) were hypoesthesia (60.5%), alopecia (55.8%), and leukopenia (55.8%). Twenty-five (58%) patients experienced grade 3 TRAEs, including hypoesthesia (23.3%) and neutropenia (14.0%). No grade 4 or grade 5 TRAEs occurred. Conclusions: RC48-ADC demonstrated a promising efficacy with a manageable safety profile in patients with HER2+ locally advanced or mUC who had failed at least one line of systemic chemotherapy. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.