Phase 2 Trial of Enfortumab Vedotin in Patients With Previously Treated Locally Advanced or Metastatic Urothelial Carcinoma in China
ABSTRACT Background Enfortumab vedotin, a fully human monoclonal antibody–drug conjugate (ADC) directed to Nectin‐4, prolonged overall survival (OS) versus standard chemotherapy in patients with previously treated locally advanced or metastatic urothelial carcinoma (mUC) previously receiving a progr...
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2024-11-01
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| Online Access: | https://doi.org/10.1002/cam4.70368 |
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| author | Siming Li Yanxia Shi Haiying Dong Hongqian Guo Yu Xie Zhongquan Sun Xiaoping Zhang Eric Kim Jun Zhang Yue Li Chenming Xu Haishan Kadeerbai Sue Lee Seema Gorla Jun Guo Xinan Sheng |
| author_facet | Siming Li Yanxia Shi Haiying Dong Hongqian Guo Yu Xie Zhongquan Sun Xiaoping Zhang Eric Kim Jun Zhang Yue Li Chenming Xu Haishan Kadeerbai Sue Lee Seema Gorla Jun Guo Xinan Sheng |
| author_sort | Siming Li |
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| description | ABSTRACT Background Enfortumab vedotin, a fully human monoclonal antibody–drug conjugate (ADC) directed to Nectin‐4, prolonged overall survival (OS) versus standard chemotherapy in patients with previously treated locally advanced or metastatic urothelial carcinoma (mUC) previously receiving a programmed cell death protein 1/ligand 1 (PD‐1/L1) inhibitor and platinum‐based chemotherapy in the pivotal, phase 3 EV‐301 clinical trial, supporting global approvals of enfortumab vedotin monotherapy. This bridging study was the first to evaluate enfortumab vedotin monotherapy in previously treated Chinese patients with locally advanced or mUC. Methods EV‐203 was a multicenter, open‐label, phase 2 study (NCT04995419) assessing efficacy, safety/tolerability, pharmacokinetics (PK), and immunogenicity of enfortumab vedotin in 40 Chinese patients (PK analysis set, n = 13) with previously treated locally advanced or mUC. Patients received enfortumab vedotin 1.25 mg/kg (Days 1, 8, and 15). Primary endpoints included confirmed objective response rate (ORR) by the independent review committee (IRC) and PK parameters of ADC, total antibody (TAb), and free monomethyl auristatin E (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; immunogenicity; and safety/tolerability. Results As of May 13, 2022, the median follow‐up was 6.5 months. Confirmed ORR was 37.5% (n/N = 15/40; 95% CI: 22.7%–54.2%) by IRC and 42.5% (n/N = 17/40; 95% CI: 27.0%–59.1%) by investigator assessment. By IRC, DCR was 72.5% (n = 29), median DOR was not reached, and median PFS was 4.7 months. Median OS was not reached. Endpoints assessed by investigators were consistent with IRC assessments. Two patients discontinued treatment for treatment‐related adverse events. No new safety signals were identified. ADC, TAb, and free MMAE were characterized in Chinese patients and consistent with previously characterized populations. The incidence of positive antitherapeutic antibodies postbaseline was 0%. Conclusion Enfortumab vedotin demonstrated meaningful clinical activity with a manageable safety profile in Chinese patients with previously treated locally advanced or mUC. Trial Registration ClinicalTrials.gov identifier: NCT04995419 |
| format | Article |
| id | doaj-art-1a50bf8eb8e543569cb07e1e31c9b6f3 |
| institution | Kabale University |
| issn | 2045-7634 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Wiley |
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| series | Cancer Medicine |
| spelling | doaj-art-1a50bf8eb8e543569cb07e1e31c9b6f32024-11-13T07:40:34ZengWileyCancer Medicine2045-76342024-11-011321n/an/a10.1002/cam4.70368Phase 2 Trial of Enfortumab Vedotin in Patients With Previously Treated Locally Advanced or Metastatic Urothelial Carcinoma in ChinaSiming Li0Yanxia Shi1Haiying Dong2Hongqian Guo3Yu Xie4Zhongquan Sun5Xiaoping Zhang6Eric Kim7Jun Zhang8Yue Li9Chenming Xu10Haishan Kadeerbai11Sue Lee12Seema Gorla13Jun Guo14Xinan Sheng15Department of Genitourinary Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing) Peking University Cancer Hospital & Institute Beijing ChinaDepartment of Medical Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine Sun Yat‐sen University Cancer Center Guangzhou ChinaDepartment of Urology Zhejiang Provincial People's Hospital Hangzhou ChinaDepartment of Urology, Drum Tower Hospital Medical School of Nanjing University, Institute of Urology, Nanjing University Nanjing ChinaDepartment of Urology, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine Central South University Hunan ChinaDepartment of Urology Huadong Hospital, Fudan University Shanghai ChinaDepartment of Hematology and Oncology (Key Department of Jiangsu Medicine) Zhongda Hospital, Southeast University Medical School Nanjing Jiangsu ChinaPfizer Inc Bothell Washington USAAstellas (China) Investment co., Ltd. Beijing ChinaAstellas (China) Investment co., Ltd. Beijing ChinaAstellas (China) Investment co., Ltd. Beijing ChinaAstellas (China) Investment co., Ltd. Beijing ChinaAstellas Pharma Inc. Northbrook Illinois USAAstellas Pharma Inc. Northbrook Illinois USADepartment of Genitourinary Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing) Peking University Cancer Hospital & Institute Beijing ChinaDepartment of Genitourinary Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing) Peking University Cancer Hospital & Institute Beijing ChinaABSTRACT Background Enfortumab vedotin, a fully human monoclonal antibody–drug conjugate (ADC) directed to Nectin‐4, prolonged overall survival (OS) versus standard chemotherapy in patients with previously treated locally advanced or metastatic urothelial carcinoma (mUC) previously receiving a programmed cell death protein 1/ligand 1 (PD‐1/L1) inhibitor and platinum‐based chemotherapy in the pivotal, phase 3 EV‐301 clinical trial, supporting global approvals of enfortumab vedotin monotherapy. This bridging study was the first to evaluate enfortumab vedotin monotherapy in previously treated Chinese patients with locally advanced or mUC. Methods EV‐203 was a multicenter, open‐label, phase 2 study (NCT04995419) assessing efficacy, safety/tolerability, pharmacokinetics (PK), and immunogenicity of enfortumab vedotin in 40 Chinese patients (PK analysis set, n = 13) with previously treated locally advanced or mUC. Patients received enfortumab vedotin 1.25 mg/kg (Days 1, 8, and 15). Primary endpoints included confirmed objective response rate (ORR) by the independent review committee (IRC) and PK parameters of ADC, total antibody (TAb), and free monomethyl auristatin E (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; immunogenicity; and safety/tolerability. Results As of May 13, 2022, the median follow‐up was 6.5 months. Confirmed ORR was 37.5% (n/N = 15/40; 95% CI: 22.7%–54.2%) by IRC and 42.5% (n/N = 17/40; 95% CI: 27.0%–59.1%) by investigator assessment. By IRC, DCR was 72.5% (n = 29), median DOR was not reached, and median PFS was 4.7 months. Median OS was not reached. Endpoints assessed by investigators were consistent with IRC assessments. Two patients discontinued treatment for treatment‐related adverse events. No new safety signals were identified. ADC, TAb, and free MMAE were characterized in Chinese patients and consistent with previously characterized populations. The incidence of positive antitherapeutic antibodies postbaseline was 0%. Conclusion Enfortumab vedotin demonstrated meaningful clinical activity with a manageable safety profile in Chinese patients with previously treated locally advanced or mUC. Trial Registration ClinicalTrials.gov identifier: NCT04995419https://doi.org/10.1002/cam4.70368antibody–drug conjugatesefficacymonomethyl auristatin Esafetyurothelial carcinoma |
| spellingShingle | Siming Li Yanxia Shi Haiying Dong Hongqian Guo Yu Xie Zhongquan Sun Xiaoping Zhang Eric Kim Jun Zhang Yue Li Chenming Xu Haishan Kadeerbai Sue Lee Seema Gorla Jun Guo Xinan Sheng Phase 2 Trial of Enfortumab Vedotin in Patients With Previously Treated Locally Advanced or Metastatic Urothelial Carcinoma in China Cancer Medicine antibody–drug conjugates efficacy monomethyl auristatin E safety urothelial carcinoma |
| title | Phase 2 Trial of Enfortumab Vedotin in Patients With Previously Treated Locally Advanced or Metastatic Urothelial Carcinoma in China |
| title_full | Phase 2 Trial of Enfortumab Vedotin in Patients With Previously Treated Locally Advanced or Metastatic Urothelial Carcinoma in China |
| title_fullStr | Phase 2 Trial of Enfortumab Vedotin in Patients With Previously Treated Locally Advanced or Metastatic Urothelial Carcinoma in China |
| title_full_unstemmed | Phase 2 Trial of Enfortumab Vedotin in Patients With Previously Treated Locally Advanced or Metastatic Urothelial Carcinoma in China |
| title_short | Phase 2 Trial of Enfortumab Vedotin in Patients With Previously Treated Locally Advanced or Metastatic Urothelial Carcinoma in China |
| title_sort | phase 2 trial of enfortumab vedotin in patients with previously treated locally advanced or metastatic urothelial carcinoma in china |
| topic | antibody–drug conjugates efficacy monomethyl auristatin E safety urothelial carcinoma |
| url | https://doi.org/10.1002/cam4.70368 |
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