P2, N=27, Recruiting, National Cancer Center, Japan

P2, N=24, Recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Jun 2026 --> Jun 2027 | Trial primary completion date: Jun 2026 --> Jun 2027

P3, N=608, Completed, Astellas Pharma Global Development, Inc. | Active, not recruiting --> Completed

The current first-line systemic treatment for metastatic bladder cancer (mBC) is chemoimmunotherapy or immunotherapy with pembrolizumab plus enfortumab vedotin (EV). No significant changes in immune cell infiltrations (CD4+, CD8+, or F4/80+) between groups may explain anti-PD-1 immunotherapy resistance. Therefore, the novel TKO metastatic model represents a useful and reproducible tool for studying tumor-cell dissemination, bone/lung metastasis, and the underlying mechanisms of anti-PD-1 immunotherapy resistance.

P2, N=25, Recruiting, Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest | Not yet recruiting --> Recruiting

P1, N=145, Recruiting, Innate Pharma | N=105 --> 145

Crucially, PET-measured target engagement predicted therapeutic outcomes more reliably than either drug dose or baseline target expression. By defining effective target engagement levels needed for optimal therapeutic outcomes, PET imaging provides a clear benchmark for dosing decisions, maximizing efficacy while potentially reducing exposure to higher, toxic doses and thereby enhancing patient safety.

P2, N=90, Recruiting, Mabwell (Shanghai) Bioscience Co., Ltd.

This exceptional case demonstrates a prolonged dual response of urothelial and lung adenocarcinomas to enfortumab vedotin. It highlights the potential role of nectin-4-targeted therapy beyond urothelial carcinoma and supports further investigation of this agent in non-small cell lung cancer.

Recent advances in targeted therapies, including FGFR inhibitors (for example, erdafitinib) and antibody‑drug conjugates (ADCs) targeting Nectin‑4 (enfortumab vedotin) and HER2 (disitamab vedotin), have reshaped treatment paradigms. The present review synthesizes current evidence on molecularly guided therapies, contrasts resistance mechanisms between FGFR inhibitors and ADCs, and evaluates strategies to overcome therapeutic limitations. By integrating translational insights and emerging preclinical data, it was aimed to provide a roadmap for optimizing biomarker‑driven approaches, novel combinations and next‑generation agents for the treatment of UC.

P1/2, N=255, Recruiting, VelaVigo Bio Inc

Monomethyl auristatin E (MMAE) is used as the cytotoxic payload for enfortumab vedotin (EV) in the treatment of locally advanced and metastatic bladder cancer (BC). In addition, the DPP4 inhibitor sitagliptin suppressed the proliferation, migration, and invasion of BC cells, and cotreatment with MMAE effectively induced cell apoptosis, arrested cells in the G2M phase of the cell cycle, increased reactive oxygen species production by inhibiting the AKT pathway, and significantly inhibited the in vivo growth of MMAE-resistant cells. This study provides insights into the use of DPP4 inhibitors as a treatment strategy for MMAE-resistant BC.