Padcev (enfortumab vedotin-ejfv)

By 2025, immunotherapy has become the therapeutic basis for UC and RCC, both in metastatic and curative treatments. In PCa and TGCT, immunotherapy options remain in the experimental phase, but research is ongoing with new combinations and biomarker-driven strategies.

Alterations in FGFR3, commonly found in the luminal-papillary molecular subtype associated with low response to immunotherapy, are the target of erdafitinib. Enfortumab vedotin, which targets Nectin-4 (expressed in >95% of urothelial carcinomas), is approved for patients who progress after chemotherapy and/or immunotherapy...Sacituzumab govitecan, an antibody-drug conjugate directed against Trop-2, is effective in basal, luminal and stroma-rich subtypes but not in neuroendocrine carcinomas. In addition, therapies developed for HER2-positive breast cancer have shown efficacy in urothelial carcinoma, with recent data from the DESTINY pan-tumour phase II trial leading to FDA approval of trastuzumab deruxtecan for HER2-overexpressing metastatic urothelial carcinoma. This paper is a comprehensive review of the molecular pathology of bladder cancer, highlighting advances in molecular classification, biomarkers and personalized therapies. The transition from morphology-based classifications to combined morphological and molecular approaches, with therapeutic implications, is also addressed.

P=N/A, N=80, Recruiting, LMU Klinikum | Trial completion date: Oct 2026 --> Feb 2027 | Trial primary completion date: Jul 2026 --> Dec 2026

P2, N=70, Recruiting, Mayo Clinic | N=50 --> 70

Further, patient-derived PDAC organoids were treated with the standard of care therapies FOLFIRINOX, gemcitabine plus paclitaxel, or the antibody-drug conjugate enfortumab vedotin...Targeting Nectin-4 with the antibody-drug conjugate enfortumab vedotin inhibited tumor growth in multiple patient-derived PDAC organoids. Collectively, our data underscores Nectin-4 as a novel therapeutic target and provides the rationale to test this agent in PDAC patients.

P1/2, N=38, Active, not recruiting, Merck Sharp & Dohme LLC | Recruiting --> Active, not recruiting

P2, N=30, Recruiting, University of Oklahoma | Not yet recruiting --> Recruiting

Recent trials demonstrate encouraging outcomes with ADC such as Enfortumab Vedotin (EV), Sacituzumab Govitecan (SG), Trastuzumab Deruxtecan (T-DXd), and Disitamab Vedotin (DV) in UC, improving response rates and Progression-Free Survival (PFS). In RCC, ADC against ENPP3, CD70, and TIM-1 show durable responses in early trials, though challenges such as dose-limiting toxicities require further investigation. Overall, this review underscores ADC as a transformative approach in uro-oncology, highlighting ongoing advancements in combination strategies and biomarker-driven applications to refine therapeutic outcomes and expand treatment options for these challenging malignancies.

P1/2, N=38, Recruiting, Merck Sharp & Dohme LLC | N=98 --> 38 | Trial completion date: Jul 2028 --> Mar 2028 | Trial primary completion date: Jul 2028 --> Mar 2028

P2, N=34, Recruiting, University of Utah | Trial completion date: Sep 2027 --> Jan 2027 | Trial primary completion date: Sep 2025 --> Jan 2026

P1, N=37, Terminated, Astellas Pharma Global Development, Inc. | N=58 --> 37 | Trial completion date: May 2028 --> Sep 2025 | Recruiting --> Terminated | Trial primary completion date: Jun 2026 --> Sep 2025; Trial was discontinued for strategic reasons. Decision was not based on safety concerns, futility, or request from regulatory authority, ethics committee, or institutional review board or EC/IRB.

P1/2, N=55, Not yet recruiting, Merck Sharp & Dohme LLC