Padcev (enfortumab vedotin-ejfv)

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

We summarize data from published studies to identify factors that influence outcomes for patients with advanced cancer of the urinary tract treated with a drug called enfortumab vedotin. An understanding of these factors can help in personalizing therapy for patients and improving their care.

Our previous work established that the elevation of ITGB4 in BLCA was closely related to cisplatin resistance...Our research also discovered a positive correlation between ITGB4 and the ADCs drug target NECTIN4, and the overexpression of ITGB4 upregulates BLCA sensitivity to enfortumab vedotin treatment. It provides a basis for the treatment choice of advanced BLCA patients with immunotherapy resistance. Collectively, these results suggest that ITGB4 may be a promising therapeutic target for advanced BLCA.

These findings identify NECTIN4 amplification as a stable, predictive biomarker that may guide treatment decisions in mUC. Data from TCGA further suggest a cross-entity relevance of NECTIN4 amplification, supporting future clinical exploration of EV in other solid tumors.

P1/2, N=106, Recruiting, Dana-Farber Cancer Institute | Enrolling by invitation --> Recruiting | Trial completion date: May 2026 --> May 2028 | Trial primary completion date: Oct 2025 --> Feb 2027

This review explored alternative treatment strategies for cisplatin-ineligible patients, including immune checkpoint inhibitors, carboplatin-based regimens, antibody-drug conjugates, and novel combination therapies. Notably, recent advancements, such as the combination of enfortumab vedotin and pembrolizumab, have shown promising survival benefits in this patient population. Additionally, emerging targeted therapies, such as fibroblast growth factor receptor inhibitors, are reshaping the treatment landscape of cisplatin-ineligible patients with MBC, emphasizing the need for personalized approaches that balance efficacy and safety.

Nectin-4 is a key therapy target in patients with advanced bladder cancer, as demonstrated by the success of enfortumab vedotin. Emerging ADC technologies and Nectin-4-targeted imaging tools could improve efficacy and patient selection, redefining both diagnostic and therapeutic approaches.