NECTIN4 (Nectin Cell Adhesion Molecule 4)

For local staging of urothelial carcinoma, mpMRI-or, in selected cases, bpMRI-should preferably be performed prior to transurethral resection of the bladder tumor (TUR-B) according to VI-RADS standards. Only in selected cases is FDG-PET/CT to be used for N/M staging and restaging. Targeted imaging (e.g., NECTIN-4) and artificial intelligence (AI) are still in the research phase, whereby prospective trials with decision-impact outcomes and standardized implementation and quality processes have priority.

P=N/A, N=50, Not yet recruiting, Shanghai Sixth People's Hospital; Shanghai Sixth People's Hospital

P1, N=444, Not yet recruiting, Fudan University Shanghai Cancer Center; CSPC Zhongqi Pharmaceutical Technology Co., Ltd.

The genomic profiles of micropapillary urothelial carcinoma overlap with those of classic urothelial carcinoma, but show higher rates of alterations in the cell cycle regulators TP53 and RB1 and the receptor tyrosine kinase ERBB2. Recently approved therapeutic agents targeting cell surface markers such as HER2 and NECTIN4 provide promising novel and potentially more effective therapies for micropapillary urothelial carcinoma.

In order to be able to use these therapeutic innovations in a targeted and precise manner in the future, biomarker-based stratification of urothelial carcinomas is likely to play a greater role. Current developments thus open up considerable potential for true precision oncology.

Important limitations remain, including limited availability of training datasets, variability in staining protocols, and regulatory challenges. Overall, ML-assisted IHC scoring is a reproducible and evolving approach that may support biomarker discovery and enhance precision GU oncology.

The pervasive absence of HER2, folate receptor alpha, DLL3, TROP-2, and nectin-4 expression in SCSTs suggests ADCs targeting these antigens may be of limited clinical benefit. The design of clinical trials investigating the use of tissue factor-targeting ADCs for the treatment of adult GCTs warrants future consideration.

These findings confirm that testicular CHC expresses Nectin-4 and may be potentially targetable with EV. Future studies are needed to verify whether metastasis and chemotherapy up-regulate Nectin-4 and increase the sensitivity to EV, and whether the absence of Nectin-4 expression by cytotrophoblasts (the proliferative population of CHC) influences its potential efficacy.

P2, N=12, Not yet recruiting, William Bradley | Initiation date: Nov 2025 --> Apr 2026

Its structure is highly complex and comprises a Bicycle connected to microtubule inhibitor monomethyl aurostatin-E (MMAE) via a molecular spacer and a cleavable linker. This provides a unique challenge in structural elucidation, and this report shows a strategy to overcome this using an incremental, nuclear magnetic resonance spectroscopy-based approach, which may be applied to complex structures of a similar nature.

Minimal tumor uptake is observed in blocking and Nectin4-negative controls, confirming specificity. Complementary fluorescence imaging further reveals the in vivo distribution of Padcev, providing valuable insights into optimal therapeutic time windows.

P1/2, N=200, Active, not recruiting, BicycleTx Limited | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Sep 2025 --> Aug 2026