Anti-tumor activity, safety and pharmacokinetics (PK) of ASG-22CE (ASG-22ME; enfortumab vedotin) in a phase I dose escalation trial in patients (Pts) with metastatic urothelial cancer (mUC).

Genitourinary (Nonprostate) Cancer
Session Type and Session Title: 
Poster Session, Genitourinary (Nonprostate) Cancer
Abstract Number: 


Poster Board Number: 
Board #156
J Clin Oncol 34, 2016 (suppl; abstr 4533)
Jonathan E. Rosenberg, Elisabeth I. Heath, Peter J. Van Veldhuizen, Jaime R. Merchan, Joshua Michael Lang, Joseph D. Ruether, Daniel Peter Petrylak, Randeep S. Sangha, David C. Smith, Srikala S. Sridhar, Elaina M. Gartner, Martha Vincent, Rong Chu, Banmeet Anand, Fernando Donate, Lynnae Jackson, Leonard M. Reyno, Jingsong Zhang; Memorial Sloan Kettering Cancer Center, New York, NY; Karmanos Cancer Institute, Wayne State University, Detroit, MI; University of Kansas Medical Center, Westwood, KS; Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL; University of Wisconsin Carbone Cancer Center, Madison, WI; Tom Baker Cancer Center, Calgary, AB, Canada; Yale University, New Haven, CT; Cross Cancer Inst, Edmonton, AB, Canada; University of Michigan, Ann Arbor, MI; Princess Margaret Cancer Centre, Toronto, ON, Canada; Seattle Genetics, Bothell, WA; Agensys Inc, Santa Monica, CA; Agensys Inc., Santa Monica, CA; Agensys, Inc, Santa Monica, CA; Agensys, Inc., Santa Monica, CA; H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL

Abstract Disclosures


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

mUC Pts only.

Dose (mg/kg)0.50.7511.25
Evaluable pts (n=28)211114
ORR, n (%)1 (50)3 (27)1 (9)2 (50)
Median Duration on Rx (Wks)




(SD/PR/CR) n (%)
2 (100)9 (82)7 (64)3 (75)

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