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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).
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 (n=28)||2||11||11||4|
|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.
Abstracts by Jonathan E. Rosenberg:
Atezolizumab (atezo) in platinum-treated locally advanced or metastatic urothelial carcinoma (mUC): Outcomes by prior therapy.Meeting: 2017 Genitourinary Cancers Symposium | Abstract No: 323
Borealis-2: A randomized phase II study of OGX-427 (apatorsen) plus docetaxel versus docetaxel alone in platinum-resistant metastatic urothelial cancer (mUC) (Hoosier Cancer Research Network GU12-160).Meeting: 2017 Genitourinary Cancers Symposium | Abstract No: 289
Characterization of POLE-mutated (POLE+) urothelial carcinoma of the bladder and urinary tract (UC).Meeting: 2017 Genitourinary Cancers Symposium | Abstract No: 387