Background: Nectin-4 is a cell adhesion molecule expressed on several tumor types, including mUC. ASG-22ME is an antibody drug conjugate (ADC) that delivers a small molecule microtubule-disrupting agent, monomethyl auristatin E (MMAE), to tumor cells expressing Nectin-4. Methods: Pts with solid tumors including mUC treated with ≥ 1 prior chemo regimen or mUC pts unfit for Cisplatin 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 (DA) were performed every 8 weeks (wks) using RECIST v 1.1. ASG-22ME was administered IV wkly for 3 out of every 4 wks until no further clinical benefit. 4 dose levels were studied: .5, .75, 1, or 1.25 mg/kg. Results: Of analyzed tumor tissues, 93% (n=243) were Nectin-4 positive (83% had H-score ≥ 150). As of 1/21/16, 39 solid tumor pts were enrolled; 31 with mUC reported here. Median age= 65 y; 100% ECOG PS ≤ 1; 21 pts (68%) had ≥ 2 lines of prior therapy for mUC. 7 pts (25%) had a PR (ORR (PR and CR) =25%), including 3/10 pts (30%) with liver metastasis. Median time on study was 15 wks. 30 pts (97%) had adverse events (AEs). The most common AE was fatigue (42%). 18 pts (58%) had Grade 3/4 AEs, with 44% considered related. 7 pts (23%) had eye disorders (Grade 1/2). 2 pts (6%) had protocol defined dose limiting toxicities. There were 2 deaths unrelated to study drug. Serum concentration of ASG-22ME decreased multi-exponentially and exposure was dose-proportional. ASG-22ME half-life is 1.5 days. Anti-tumor activity was seen at all dose levels. The median progression free survival is 17 wks (unplanned exploratory analysis). Enrollment is open at active dose levels: updated results will be presented. Conclusions: ASG-22ME targeting Nectin-4 is an ADC in mUC that is well tolerated and active. These results warrant ongoing study of ASG-22ME in mUC pts. Clinical trial information: NCT02091999

Evaluable pts = ≥ 1 dose of drug and ≥ 1 post-baseline DA.