A Study of Escalating Doses of ASG-22CE Given as Monotherapy in Subjects With Metastatic Urothelial Cancer and Other Malignant Solid Tumors That Express Nectin-4

Astellas Pharma Global Development, Inc.
Study Design: 
This is a Phase I, single arm clinical trial of patients with mUC treated with 1 or more prior chemotherapy regimens or who were cisplatin-ineligible. In this analysis, patients with mUC treated at the recommended phase 2 dose (RP2D) were analyzed.
Patients with metastatic urothelial cancer (mUC) have a poor prognosis despite the approval of several immunotherapy agents. Therefore, this trial evaluates the use of a novel antibody-drug conjugate, ASG-22CE also known as enfortumab vedotin, in mUC patients. The drug targets Nectin-4 which is overexpressed in urothelial tumors and the conjugate binds to Nectin-4 and delivers a microtubule disrupting toxin.
The primary endpoint was tolerability and antitumor efficacy was the secondary endpoint.
This trial presents a unique and novel therapy for mUC patients who have not only failed prior platinum chemotherapy but also has activity in patients who have failed prior checkpoint inhibitor therapy and even have liver metastases. The data are still not yet mature but the preliminary data presented at ASCO 2018 are intriguing.
Data as of January 2018 was presented at this year’s ASCO meeting (Abstract #4504), 155 mUC patients accrued of whom 112 received ASG-22CE at the RP2D. This was a heavily pre-treated cohort with aggressive disease evidenced by the following: 81% of patients received prior platinum chemotherapy, 60% received two or more prior therapies for metastatic disease, and 29% of patients had liver metastases. Furthermore, 84 patients (75%) had received a checkpoint inhibitor. Overall, the treatment was highly tolerable with grade ≤2 fatigue being the most commonly seen adverse event (AE) in 50%. Four patients however did experience a fatal treatment-related AE including respiratory failure, urinary tract obstruction, diabetic ketoacidosis, and multi-organ failure. The overall response rate (ORR) was 33% with 3 complete responses and 34 partial responses. Response rates were 32% in patients previously treated with checkpoint inhibitor vs. 37% in checkpoint inhibitor-naïve patients. The median overall survival was 12.5 months.