EV-201: Results of enfortumab vedotin monotherapy for locally advanced or metastatic urothelial cancer previously treated with platinum and immune checkpoint inhibitors.

Abstract

4505 Background: Locally advanced or metastatic urothelial cancer (la/mUC) remains a lethal disease with limited treatment options for patients (pts) who progress on or after platinum and/or checkpoint inhibitor (CPI). Enfortumab vedotin (EV) is an antibody-drug conjugate targeting Nectin-4, which is highly expressed in UC. EV-201 is a pivotal, single-arm, two-cohort study of EV in la/mUC patients with prior CPI and platinum-containing chemotherapy (Cohort 1) or a CPI and no prior chemotherapy (Cohort 2). Here, we present preliminary data from Cohort 1. Methods: Pts in this open-label, multicenter study received 1.25 mg/kg EV on Days 1, 8, and 15 of each 28-day cycle. The primary endpoint was confirmed ORR per RECIST 1.1 by blinded independent central review. Secondary endpoints are duration of response, PFS, OS, safety/tolerability. Results: Between Oct 2017 and Jul 2018, EV-201 enrolled 128 pts in Cohort 1 (la/mUC pts previously treated with platinum and a CPI), 125 of whom were treated with EV (70% male; median age 69 y [range 40–84 y]; 34% upper tract; a median of 2 prior systemic therapies). As of 03 Jan 2019, the confirmed ORR was 42% (95% CI: 33.6%–51.6%), with 9% CR. The ORR in CPI non-responders was 38% (95% CI: 27.3%–49.2%), and 36% (95% CI: 22.9%–50.8%) in pts with liver metastases (LM). Most common treatment-related AEs, as determined by investigators, included fatigue (50%), alopecia (48%), and decreased appetite (41%). Treatment-related AEs of interest include any rash (48% all grade, 11% ≥ G3) and any peripheral neuropathy (50% all grade, 3% ≥ G3). One death was reported as treatment related by the investigator (interstitial lung disease), but was confounded by a suspected pulmonary infection. Conclusions: Preliminary results from this EV pivotal study demonstrated a clinically meaningful ORR, consistent with the phase 1 trial, in la/mUC pts with prior platinum and CPI, including LM pts, where there is a high unmet need. EV was well tolerated with a manageable safety profile in these pts. Updated data, including duration of response, PFS, and OS will be presented. Clinical trial information: NCT03219333.