Background: SLITRK6 is a cell adhesion molecule highly expressed on several tumors, including mUC. ASG-15ME is an antibody drug conjugate (ADC) that delivers a small molecule microtubule-disrupting agent, monomethyl auristatin E (MMAE), to tumor cells expressing SLITRK6. Methods: mUC pts unselected for SLITRK6 expression (determined by an IHC assay) and previously treated with ≥ 1 prior chemo regimen or unfit for Cisplatin were enrolled using a modified continual reassessment method design. Disease assessments (DA) were performed every 8 weeks (wks) using RECIST v 1.1. ASG-15ME was administered IV weekly for 3 out of every 4 wks until no further benefit. 6 dose levels were studied: 0.1, .25, .5, 0.75, 1, or 1.25 mg/kg. Results: Of analyzed tumor tissues, 85% (n=46) were SLITRK6 positive (56% had H-score ≥150). As of 1/21/16, 43 pts were enrolled. Anti-tumor activity was seen at dose levels ≥ 0.5 mg/kg (n=37 reported here). Median age= 64 y; 100% ECOG PS ≤ 1; 22 pts (56%) had ≥ 2 lines of prior therapy. 1 pt had a confirmed complete response (CR) and 10 pts had partial response (PR) (ORR (PR and CR) =30%) including 3/10 pts (30%) with liver metastases. Median time on study was 14 wks. 37 pts (95%) had adverse events (AEs). The most common AE was fatigue (56%). 20 pts (51%) had Grade 3/4 AEs with 35% considered related. 9 pts (23%) had eye disorders (1 Gr 3). 4 pts (11%) had protocol defined dose limiting toxicities. There were 2 deaths unrelated to study drug. Serum concentrations of ASG-15ME decreased multi-exponentially and exposure was dose-proportional. ASG-15ME half-life is 2.3 days. The median progression free survival is 16 wks (unplanned exploratory analysis). Enrollment is open at active dose levels; updated results will be presented. Conclusions: ASG-15ME targeting SLITRK6 is an ADC in mUC that is well tolerated and active. These results warrant ongoing study of ASG-15ME in mUC pts. Clinical trial information: NCT01963052

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