Padcev (enfortumab vedotin-ejfv)

EV with pembrolizumab demonstrated promising clinical activity as first-line treatment in patients with PD-L1 CPS ≥1 R/M HNSCC. Safety results reinforced the manageable tolerability profile of EV with pembrolizumab.

P3, N=390, Not yet recruiting, Astellas Pharma Global Development, Inc.

The second case involves a patient with metastatic micropapillary urothelial carcinoma with HER2 expression, refractory to platinum chemotherapy, avelumab maintenance, and enfortumab vedotin. These two observations illustrate the capacity of T-DXd to induce deep and complete metabolic remissions in distinct HER2-altered solid tumors. They support further development of HER2-targeted ADCs beyond traditional indications and highlight the value of FDG-PET/CT for assessing the depth of response to these agents.

Enfortumab vedotin plus pembrolizumab established the new first-line standard for metastatic UC, achieving a median overall survival of 33.8 months versus 15.9 months (hazard ratio [HR] 0.51, 95% confidence interval 0.43-0.61)...Critically, the IMvigor011 trial has now provided Level 1b evidence that ctDNA-guided adjuvant atezolizumab improves both disease-free survival (DFS) (HR 0.64, p = 0.0047) and OS (HR 0.59, p = 0.0131) in ctDNA(+) patients, while validating treatment de-escalation in ctDNA(-) patients (1-year DFS 95%). Erdafitinib in patients harboring FGFR2/3 alterations (HR 0.64) confirms the value of genomic profiling...In conclusion, dynamic precision oncology has transformed UC management, with the IMvigor011 trial establishing ctDNA-guided MRD status as the first phase 3-validated predictive biomarker framework for adjuvant therapy selection in a solid tumor. Implementation requires adherence to established standardization frameworks, cross-platform and cross-agent validations, and tiered implementation strategies to ensure equitable access across diverse resource settings.

P1/2, N=390, Active, not recruiting, Merck Sharp & Dohme LLC | Completed --> Active, not recruiting | N=49 --> 390

Maleimide-linked antibody-drug conjugates (ADC) like Enfortumab Vedotin (EV) have limited in vivo drug-linker stability...Cys2-N4MU01-PMMAE warrants further optimization to enhance its effectiveness against TNBC models. This study also re-enforces the rationale for the development of novel moderate affinity and highly stable targeted therapeutics against other cancers.

P1, N=32, Recruiting, Emory University | Trial completion date: Dec 2026 --> Dec 2028 | Trial primary completion date: Nov 2026 --> Nov 2027

P2/3, N=197, Not yet recruiting, Eli Lilly & Co.

P1/2, N=55, Recruiting, Merck Sharp & Dohme LLC | Trial completion date: Oct 2030 --> Jul 2031 | Trial primary completion date: Oct 2030 --> Jul 2031

P2, N=55, West China Hospital of Sichuan University; West China Hospital of Sichuan University

Key advances include: (1) In bladder cancer, perioperative durvalumab (NIAGARA) and enfortumab vedotin plus pembrolizumab (KEYNOTE-905/EV-303) set new standards, while HER2-targeted disitamab vedotin plus toripalimab (RC48-C016) improved metastatic survival...(3) In prostate cancer, enzalutamide plus leuprolide improved survival in high-risk biochemical recurrence (EMBARK). Capivasertib plus abiraterone benefited PTEN-deficient metastatic hormone-sensitive disease (CAPItello-281). The PSMAddition trial demonstrated that adding [177Lu]Lu-PSMA-617 to standard therapy significantly improved radiographic PFS in PSMA-positive mHSPC. Docetaxel scheduling was optimized (ARASAFE), and an AI model (STAMPEDE) identified patients for AR inhibitor benefit. Novel agents like saruparib and pasritamig showed promise...The 2025 evidence establishes multiple new standards of care across GU cancers, emphasizing biomarker-driven strategies, immunotherapy integration, novel resistance mechanisms, and treatment optimization. This synthesis provides an evidence-based framework for updating guidelines and highlights the move toward more personalized management, while noting persistent challenges and future research needs.

P2, N=25, Recruiting, Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest