Interim analysis of a phase I dose escalation trial of ASG-22CE (ASG-22ME; enfortumab vedotin), an antibody drug conjugate (ADC), in patients (Pts) with metastatic urothelial cancer (mUC)

Abstract

Background: Nectin-4 is a protein expressed on several tumors, including mUC. Enfortumab vedotin is an ADC that delivers a small molecule microtubule-disrupting agent, monomethyl auristatin E (MMAE), to tumors expressing Nectin-4. Methods: Pts with solid tumors, including mUC, treated with >= 1 prior chemo were enrolled using a modified continual reassessment method design. Pts were prescreened for Nectin-4 expression (IHC assay) and enrolled if H-score >=150. Disease assessments were performed every 8 weeks (wks) using RECIST v 1.1. Enfortumab vedotin was administered IV wkly for 3 out of every 4 wks. 4 dose levels were studied: 0.5, 0.75, 1, or 1.25 mg/kg. Results: As of 4/29/16, 49 solid tumor pts were enrolled; 42 with mUC reported here. Of analyzed tumor tissues, 98% were Nectin-4 positive (93% had H-score >= 150). Median age 67 y; 100% ECOG PS = 2 prior therapies (tx). Of 33 response evaluable pts, 10 had a partial response (PR) (ORR =30%), including 4/ 10 pts (40%) with liver metastasis and 3/12 (25%) who failed checkpoint inhibitor tx. Antitumor activity is seen at all dose levels. Median duration on treatment is 12 wks. Both median progression free survival and duration of response are 16 wks. 38 pts (91%) had adverse events (AEs). The most common tx related AE was fatigue (38%). 23 pts (55%) had Grade (G) 3/4 AEs, 10 pts (24%) considered related. 9 pts (21%) had ocular AEs (G1/2). 2 pts had protocol defined dose limiting toxicities. There were 2 deaths, unrelated to tx. Serum concentration of enfortumab vedotin decreased multi-exponentially with half-life ~1.6 days. Exposure was dose proportional. Expansion cohorts are open at 1.25 mg/kg: updated results will be presented. Conclusions: This novel Nectin-4 targeted ADC, enfortumab vedotin, is well tolerated in mUC pts with encouraging antitumor activity. These results warrant further studies in mUC. (Table Presented).