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

person Siming Li Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Genitourinary Oncology, Peking University Cancer Hospital and Institute, Beijing, China info_outline Siming Li, Yanxia Shi, Haiying Dong, Hongqian Guo, Yue Li, Haishan Kadeerbai, Chenming Xu, Eric Kim, Sue Lee, Seema Rao Gorla, Jun Zhang, Jun Guo, Xinan Sheng

Authors person Siming Li Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Genitourinary Oncology, Peking University Cancer Hospital and Institute, Beijing, China info_outline Siming Li, Yanxia Shi, Haiying Dong, Hongqian Guo, Yue Li, Haishan Kadeerbai, Chenming Xu, Eric Kim, Sue Lee, Seema Rao Gorla, Jun Zhang, Jun Guo, Xinan Sheng Organizations Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Genitourinary Oncology, Peking University Cancer Hospital and Institute, Beijing, China, Sun yat-sen University Cancer Center, Guangzhou, China, Department of Urology, Zhejiang Provincial People's Hospital, Hangzhou, China, Nanjing Drum Tower Hospital, Nanjing, China, Astellas (China) Investment Co., Ltd, Beijing, China, Seagen, Bothell, WA, Astellas Pharma, Inc., Northbrook, IL, Astellas Pharma Inc., Northbrook, IL, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Genitourinary Oncology, Peking University Cancer Hospital & Institute, Collaborative Innovation Center of Cancer Medicine, Beijing, China Abstract Disclosures Research Funding Pharmaceutical/Biotech Company Astellas Pharma, Inc. and Seagen Inc. 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.

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