Novel ADCs and combination therapy in urothelial carcinoma - latest updates from the 2023 ASCO-GU Cancers Symposium

Sep 24, 2026

Antibody–drug conjugates (ADCs) combine targeted antibody delivery with potent cytotoxic payloads, making them a major research focus in anti-tumor drug development. The article synthesizes notable advances and clinical data from the 2023 ASCO-GU Cancers Symposium related to ADCs for urothelial carcinoma. Key updates include efficacy and safety outcomes for enfortumab vedotin, including responses in cisplatin-ineligible patients and treatment-related adverse events, and additional ongoing clinical study directions discussed for ADC strategies.

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Novel ADCs and combination therapy in urothelial carcinoma

Enfortumab vedotin in urothelial carcinoma

Sacituzumab govitecan in urothelial carcinoma

Table 1: Characteristics of ADCs for the treatment of urothelial carcinoma

Yu etal. Journal of Hematology & Oncology (2023) 16:85 [https://doi.org/10.1186/s13045-023-01475-9](https://doi.org/10.1186/s13045-023-01475-9) Journal of Hematology & Oncology CORRESPONDENCE Open Access Novel ADCs and combination therapy in urothelial carcinoma: latest updates from the 2023 ASCO-GU Cancers Symposium Jiazheng Yu1†, Siyu Wu1†, Rong Li1†, Yuanhong Jiang1, Jianyi Zheng1, Zeyu Li1, Mingyang Li1, Kerong Xin1, Xiaojiao Guan2*, Shijie Li1* and Xiaonan Chen1* Abstract Antibody–drug conjugates (ADCs) combine the cytotoxicity of small-molecule drugs with antibody targeting. Due to their precise and powerful effect, they have become a new hotspot and an important trend in the research and development of anti-tumor antibody drugs. Every year, exciting new developments and innovations in the treatment of urological tumors are introduced at the American Society of Clinical Oncology-Genitourinary (ASCO-GU) Cancers Symposium. In this article, we summarize some of the most impressive advances in new clinical trials and clinical data on ADCs in the 2023 ASCO-GU Cancers Symposium for the treatment of urothelial carcinoma. Keywords ADCs, Enfortumab vedotin, Sacituzumab govitecan, Disitamab vedotin, Urothelial carcinoma To the editor: Each year, exciting developments in urological tumors are introduced at the American Society of Clinical Oncology-Genitourinary (ASCO-GU) Cancers Symposium. In this article, we review the impressive progress made in new clinical trials and data concerning antibody–drug conjugates (ADCs) for urothelial carcinoma treatment from the 2023 Symposium. †Jiazheng Yu, Siyu Wu and Rong Li contributed equally to this work. *Correspondence: Xiaojiao Guan [guanxiaojiao@126.com](guanxiaojiao@126.com)[ ](guanxiaojiao@126.com)Shijie Li [sjli@cmu.edu.cn](sjli@cmu.edu.cn)[ ](sjli@cmu.edu.cn)Xiaonan Chen[chenxn@cmu.edu.cn](chenxn@cmu.edu.cn) 1 Department of Urology, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning, People’s Republic of China 2 Department of Pathology, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning, People’s Republic of China Enfortumab vedotin in urothelial carcinoma Enfortumab vedotin (EV) is an ADCs formed by joining a humanized Nectin-4 targeted IgG1 monoclonal antibody, enfortumab, and a microtubule-disrupting agent, monomethyl auristatin E (MMAE), through acleavable mc-val-cit-PABC linker. The EV-103 cohort K (NCT03288545) evaluated EV or EV + Pembrolizumab (Pembro) as a first-line therapy for cisplatinineligible patients with locally advanced or metastatic urothelial cancer (la/mUC) . Patients were randomized 1:1 to receive EV monotherapy on days 1 and 8, orin combination with Pembro on day 1 of the 3-week cycles. EV monotherapy showed an objective response rate (ORR) of 45.2% (95% CI 33.5–57.3), while the EV + Pembro combination demonstrated an ORR of 64.5%(95% CI 52.7–75.1) . Treatment-related adverse events (TRAEs) in the EV + Pembro arm included skin reactions (67.1%) and peripheral neuropathy (60.5%) . TRAEs were observed in 68.4% of the patients. This led to the interruption of EV or Pembro, with 48.7% of patients requiring EV dose reduction [1] . This established the foundation for accelerated approval of EV © The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the per

FAQs

What are antibody–drug conjugates (ADCs) and why are they important in cancer drug development?

ADCs link targeted antibody delivery with cytotoxic small-molecule drugs. Their precise and powerful effects have made them a major hotspot and important trend in anti-tumor antibody drug R&D.

What did the EV-103 cohort K evaluate for urothelial carcinoma patients?

EV-103 cohort K evaluated enfortumab vedotin (EV) alone or EV plus pembrolizumab as first-line therapy for cisplatin-ineligible patients with locally advanced or metastatic urothelial cancer.

What safety and response highlights are reported for EV alone versus EV plus pembrolizumab?

EV monotherapy showed an objective response rate of 45.2%, while EV plus pembrolizumab showed 64.5%. Treatment-related adverse events in the combination arm included skin reactions and peripheral neuropathy, with a substantial proportion of patients experiencing treatment-related adverse events.

Sep 24, 2026

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