EV-203: Phase 2 trial of enfortumab vedotin in patients with previously treated advanced urothelial carcinoma in China.

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e16574 Background: Enfortumab vedotin (EV), a fully human monoclonal antibody directed against Nectin-4 delivering intracellular monomethyl auristatin E (MMAE) to tumor cells, demonstrated superior overall survival (OS) with manageable safety/tolerability over standard chemotherapy in patients (pts) with previously treated locally advanced or metastatic urothelial carcinoma (la/mUC) in the pivotal EV-301 trial. EV-301 findings led to approval in 41 countries. As EV monotherapy has not been studied in a Chinese population, EV-203 (NCT04995419) assessed efficacy, safety/tolerability, and pharmacokinetics (PK) of EV in pts with la/mUC in China. Methods: In this single-arm, open-label, phase 2 study, Chinese pts with la/mUC previously treated with platinum-based chemotherapy and PD-1/L1 inhibitor therapy received EV 1.25 mg/kg via intravenous infusion on days 1, 8, and 15 of each 28-d cycle at 6 centers. Pts had Eastern Cooperative Oncology Group performance status 0–1 and were excluded if they had preexisting grade ≥2 sensory/motor neuropathy, active central nervous system metastases, clinically significant toxicity associated with prior treatment, or history of uncontrolled diabetes mellitus. Two study centers enrolled pts for a PK cohort. Primary endpoints were confirmed objective response rate (ORR; by Response Evaluation Criteria in Solid Tumors v1.1) by independent review committee (IRC) and PK parameters of antibody–drug conjugate (ADC), total antibody (TAb), and unconjugated MMAE. Secondary endpoints included investigator-assessed confirmed ORR; investigator-/IRC-assessed duration of response (DOR), disease control rate (DCR), and progression-free survival (PFS); OS; and safety/tolerability. Results: A total of 40 Chinese pts were enrolled; 15 were in the PK cohort. Confirmed ORR by IRC was 37.5% (n/N=15/40; 95% CI: 22.7–54.2); best overall response was complete response for 1 (2.5%) pt and partial response for 14 (35.0%) pts. Investigator-assessed ORR was 42.5% (n=17). DCRs were 82.5% (n=33) by investigator and 72.5% (n=29) by IRC. Median DOR by investigator and IRC were not reached. Median PFS were 4.24 mo by investigator and 4.67 mo by IRC. Median follow-up time was 6.5 mo and median OS was not reached. Most treatment-related adverse events (TRAEs) were grade 1–2. Two pts discontinued EV due to TRAE (acute coronary syndrome and hyperglycemia/rash). Serum ADC and TAb concentrations peaked at end of EV infusion; MMAE concentrations had median peak 2–3 d post dose. Minimal ADC, TAb, and MMAE accumulation were observed with repeat EV dosing. Conclusions: EV-203 results show EV has a favorable benefit–risk profile, demonstrating meaningful clinical activity with a manageable safety profile, in pts with previously treated la/mUC in China. EV data are consistent with those from the global population in phase 2–3 EV trials of la/mUC. No new safety signals were identified. Clinical trial information: NCT04995419 .