Padcev (enfortumab vedotin-ejfv) / Astellas, Pfizer - LARVOL DELTA

Case Report: Mature tertiary lymphoid structures in a metastatic urothelial carcinoma patient with an exceptional response to sequential immune checkpoint inhibitor and antibody-drug conjugate therapy. (PubMed, Front Oncol) - "A 77-year-old man with bladder cancer and lung metastases experienced disease progression after two cycles of gemcitabine/cisplatin. Pembrolizumab was initiated but discontinued after a single dose due to destructive thyroiditis; nevertheless, his lung metastases subsequently regressed. Because residual urothelial disease persisted in the bladder, enfortumab vedotin (EV) was initiated...In an exploratory cohort of six additional sequentially treated mUC cases evaluated using the same methodology, mTLS were not detected, even among cases exhibiting a generalized T-cell infiltration. Pre-existing mTLS identified in routine TUR specimens reflect a highly compartmentalized immune niche-distinct from a simple "hot tumor" phenotype-that may help predict which patients are likely to achieve a durable benefit from sequential ICI and ADC therapy, potentially informing treatment selection and sequencing in mUC."

Checkpoint inhibition • IO biomarker • Journal • Bladder Cancer • Endocrine Disorders • Fatigue • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer • BCL6 • CD20 • CD21 • CD4 • CD8

Incidence and risk factors for pneumonitis in urothelial carcinoma treated with enfortumab vedotin plus pembrolizumab: retrospective study. (PubMed, Oncologist) - "Pneumonitis occurred in 7.0% of EVP-treated patients and generally arose early. Prior ICI exposure predicted pneumonitis, particularly grade ≥2 events, which were associated with increased mortality; any-grade pneumonitis and PFS were not."

Journal • Retrospective data • Infectious Disease • Oncology • Pneumonia • Respiratory Diseases • Solid Tumor • Urothelial Cancer

Is This the End of the Cisplatin Eligibility Era in Muscle-invasive Bladder Cancer? Letter in reference to: Matthew D. Galsky, Begoña P. Valderrama, Marco Maruzzo, et al. Enfortumab vedotin and pembrolizumab in cisplatin-eligible bladder cancer. N Engl J Med 2026;395:338-48. doi:10.1056/NEJMoa2601486; and Galsky MD, Hahn NM, Rosenberg J, et al. A consensus definition of patients with... (PubMed, Eur Urol) - No abstract available

Journal • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer

PlugIN: PLUG-IN: Pembrolizumab Combined With Enfortumab Vedotin for Advanced Melanoma Patients (clinicaltrials.gov) - P2 | N=60 | Active, not recruiting | Sponsor: Grupo Español Multidisciplinar de Melanoma | Recruiting ➔ Active, not recruiting

Enrollment closed • Melanoma • Oncology • Solid Tumor • BRAF • PD-L1

STAR-EV: Enfortumab Vedotin and Stereotactic Radiation for Localized, Cisplatin Ineligible Muscle Invasive Bladder Cancer (clinicaltrials.gov) - P1/2 | N=19 | Recruiting | Sponsor: University of Texas Southwestern Medical Center | Trial completion date: Jul 2027 ➔ Sep 2029 | Trial primary completion date: Jul 2026 ➔ Sep 2028

Trial completion date • Trial primary completion date • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor

Enfortumab vedotin-related cutaneous toxicity: Clinical features, pathogenesis and management. (PubMed, J Dermatol Sci) - "This review summarizes the molecular structure and function of nectin-4 and the clinical and histopathologic features of EV-related cutaneous toxicity and discusses current approaches to management. By integrating mechanistic insights from experimental studies with clinical and histopathologic observations, this review provides a translational framework to support optimal recognition and management of EV-related cutaneous toxicity."

Journal • Review • Oncology • Solid Tumor • Steven-Johnson Syndrome • Urothelial Cancer • NECTIN4

Enfortumab Vedotin, Pembrolizumab and Quemliclustat for the Treatment of Unresectable Locally Advanced and Metastatic Urothelial Cancer (clinicaltrials.gov) - P1/2 | N=27 | Recruiting | Sponsor: Fred Hutchinson Cancer Center | Not yet recruiting ➔ Recruiting

Enrollment open • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer

Merck Receives Positive EU CHMP Opinion for KEYTRUDA (pembrolizumab) Plus Padcev (enfortumab vedotin-ejfv) as Perioperative Treatment for Adults With Resectable Muscle-Invasive Bladder Cancer (MIBC) (Businesswire) - "This recommendation, which also includes KEYTRUDA SC [known as KEYTRUDA QLEX (pembrolizumab and berahyaluronidase alfa-pmph) in the U.S.], will now be reviewed by the European Commission (EC) for marketing authorization in the European Union (EU), Iceland, Liechtenstein and Norway. A final decision is expected by the fourth quarter of 2026....The recommendation is based on results from the Phase 3 KEYNOTE-B15 trial (also known as EV-304), which was conducted in collaboration with Pfizer and Astellas."

CHMP • EMA approval • Bladder Cancer

Study EV-103 dose escalation/cohort A (DE/A): 5y follow-up of first-line (1L) enfortumab vedotin (EV) + pembrolizumab (P) in cisplatin (CIS)-ineligible locally advanced or metastatic urothelial carcinoma (la/mUC) (ESMO 2024) - P1/2 | "In EV-103, pts treated with 1L EV+P continued to show durable responses and meaningful survival after 5y follow-up, with a generally manageable and stable safety profile. An unprecedented 41.5% of pts treated are alive at 5y, which dramatically exceeds historical data (EORTC 30986). These results further support tx with EV+P as 1L SoC in la/mUC."

Clinical • Metastases • Oncology • Solid Tumor • Urothelial Cancer

Study EV-103: Neoadjuvant treatment with enfortumab vedotin monotherapy in cisplatin-ineligible patients with muscle invasive bladder cancer (MIBC)—2-year event-free survival and safety data for Cohort H. (ASCO 2024) - P1/2 | "Research Funding: Seagen Inc., Bothell, WA, USA, which was acquired by Pfizer in Dec. Neoadjuvant EV monotherapy treatment showed promising results for antitumor activity and 2-year EFS with a manageable safety profile in cisplatin-ineligible pts with MIBC. These results support ongoing phase 2 and 3 programs in MIBC evaluating EV alone or combined with pembrolizumab (EV-103 Cohort L, KN-905/EV-303, KN-B15/EV-304)."

Clinical • Monotherapy • Alopecia • Anemia • Bladder Cancer • Constipation • Fatigue • Gastroenterology • Gastrointestinal Disorder • Genito-urinary Cancer • Hematological Disorders • Immunology • Oncology • Pain • Solid Tumor • Urothelial Cancer • NECTIN4

Prophylactic intravenous dexamethasone is associated with reduced cutaneous toxicity during first-line enfortumab vedotin plus pembrolizumab for locally advanced or metastatic urothelial carcinoma: a multicenter prospective cohort study. (PubMed, Int J Clin Oncol) - "An institutional dexamethasone-premedication strategy was associated with reduced cutaneous toxicity during first-line enfortumab vedotin plus pembrolizumab. Exploratory analyses found no significant differences in response or PFS; adequately powered studies with longer follow-up should determine whether dexamethasone premedication affects antitumor efficacy."

Journal • Oncology • Solid Tumor • Urothelial Cancer

Sequential Antibody-Drug Conjugate Therapy with Enfortumab Vedotin and Sacituzumab Govitecan in Metastatic Urothelial Carcinoma: A Systematic Review and Meta-Analysis (ESMO 2026) - No abstract available

ADC • Metastases • Retrospective data • Review • Oncology • Solid Tumor • Urothelial Cancer

Enfortumab vedotin (EV) with pembrolizumab (P) versus chemotherapy (chemo) in previously untreated locally advanced or metastatic urothelial carcinoma (la/mUC): Analysis of the cisplatin (cis)-ineligible population from EV-302/KEYNOTE-A39. (ASCO 2024) - P3 | " Pts with previously untreated la/mUC were randomized 1:1 to receive 3-week cycles of EV (1.25 mg/kg IV; Days 1 and 8) and P (200 mg IV; Day 1) or PBC (gemcitabine with cis or carboplatin [carbo])...52 pts received maintenance avelumab; 58 pts received PD-1/L1 therapy as second-line tx... In this pt population with historically poor prognosis, EV+P improved clinical outcomes in pts who were ineligible for cis; results were consistent with the overall population. The risk of death was reduced by more than 50%. The AE profile of EV+P was generally manageable with no new safety signals."

Clinical • Metastases • Diabetes • Hepatology • Inflammation • Oncology • Pain • Pneumonia • Solid Tumor • Urothelial Cancer

Enfortumab Vedotin (EV) With or Without Pembrolizumab (P) as First-Line (1L) Treatment for Cisplatin (cis)-Ineligible Locally Advanced Or Metastatic Urothelial Carcinoma (la/mUC): Long-Term Follow-up Analysis from EV-103 Cohorts DE/A and K (ESMO 2026) - No abstract available

Clinical • Metastases • Oncology • Solid Tumor • Urothelial Cancer

Outcomes of Pembrolizumab + Enfortumab Vedotin in the SATURNO study (Multicenter, proSpective, non-interventional Italian registry of advanced/meTastatic Urothelial carcinoma). A FICOG and Meet-URO study. (ESMO 2026) - No abstract available

Clinical • Metastases • Oncology • Solid Tumor • Urothelial Cancer

Enfortumab Vedotin and Pembrolizumab in Untreated Advanced Urothelial Cancer. (PubMed, N Engl J Med) - P3 | "Treatment with enfortumab vedotin and pembrolizumab resulted in significantly better outcomes than chemotherapy in patients with untreated locally advanced or metastatic urothelial carcinoma, with a safety profile consistent with that in previous reports. (Funded by Astellas Pharma US and others; EV-302 ClinicalTrials.gov number, NCT04223856.)."

Journal • Metastases • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer

Treatment Patterns and Outcomes After Recurrence Following Adjuvant Nivolumab for Urothelial Carcinoma: An AGEHA Real-World Study. (PubMed, Int J Urol) - "Recurrence after adjuvant nivolumab occurred in 28% of patients in real-world practice. Post-recurrence management was heterogeneous, and EV-based therapy was frequently used in this setting. These findings provide hypothesis-generating real-world evidence on treatment sequencing after adjuvant nivolumab and require validation in larger cohorts with longer follow-up."

Journal • Real-world evidence • Retrospective data • Oncology • Solid Tumor • Urothelial Cancer

Meta-analysis of platinum chemotherapy combinations with immunotherapy in metastatic urothelial carcinoma. (PubMed, Oncologist) - "The therapeutic landscape for metastatic urothelial carcinoma (mUC) has evolved significantly due to the development of innovative combination treatments, including enfortumab vedotin-pembrolizumab (EVP)...The meta-analysis showed that cisplatin-gemcitabine plus IO combination and carboplatin-gemcitabine plus IO combination improve progression-free survival compared to platinum-gemcitabine therapy (hazard ratio [HR] = 0.71, 95% CI: 0.62-0.82; P < .0001 and HR = 0.85, 95% CI: 0.73-0.98; P < .03, respectively)...In summary, combining cisplatin-gemcitabine with immunotherapy offers significant overall survival benefits in mUC. The exact mechanisms-whether cisplatin's immunomodulatory effects or patient demographic differences-are yet to be determined, necessitating further research to understand these outcomes better."

Journal • Metastases • Retrospective data • Oncology • Solid Tumor • Urothelial Cancer

Study EV-104: Phase 1 study of intravesical enfortumab vedotin for treatment of patients with non-muscle invasive bladder cancer (NMIBC) (Trial in Progress) (EAU 2022) - P1 | "However, most patients are reluctant to undergo radical cystectomy and their options are limited to intravesical chemotherapy or pembrolizumab. Safety and antitumor activity endpoints will be summarized using descriptive statistics. Sites are planned in the US, Canada, and EU."

Clinical • P1 data • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer • NECTIN4

Concomitant medications in patients with metastatic urothelial carcinoma receiving enfortumab vedotin: real-world data from the ARON-2EV study. (PubMed, Clin Exp Metastasis) - P | "In our study we evaluated the association of concomitant use of antibiotics (ATBs), proton pump inhibitors (PPIs), corticosteroids, statins, metformin and insulin with patient outcomes and we validated the prognostic role of a concomitant drug score in mUC patients treated with enfortumab vedotin (EV) monotherapy. In the Cox multivariate analysis, the concomitant drug score was a significant factor predicting both OS (HR = 1.32 [95% CI 1.03 - 1.68], p = 0.026) and PFS (HR = 1.23 [95% CI 1.01 - 1.51], p = 0.044). Our findings suggest detrimental impact of concomitant use of ATBs and corticosteroids on survival outcomes and the prognostic utility of the concomitant drug score in previously treated mUC patients receiving EV."

Journal • Real-world evidence • Retrospective data • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer

Neoadjuvant stereotactic radiotherapy and enfortumab vedotin: A phase I/II study for localized, cisplatin ineligible, muscle invasive bladder cancer (STAR-EV). (ASCO 2025) - P1/2 | "Serum and urinary biomarkers will be explored. The study is open and enrolling (NCT06394570)."

Clinical • P1/2 data • Bladder Cancer • Genito-urinary Cancer • Oncology • Pain • Solid Tumor • Urothelial Cancer

Real-world prognostic assessment of the HERO score in metastatic urothelial carcinoma treated with enfortumab vedotin (ARON-2EV study). (PubMed, ESMO Open) - "In this large international real-world cohort, the HERO score was associated with survival and response outcomes in patients with mUC treated with EV, particularly through identification of a subgroup with a more favorable prognosis (score 2). However, discrimination between lower score categories was less pronounced. Further prospective refinement and evaluation of the HERO score are warranted, particularly in contemporary EV-based treatment strategies."

Journal • Real-world evidence • Oncology • Solid Tumor • Urothelial Cancer

INCIDENCE AND RISK FACTORS FOR PNEUMONITIS IN PATIENTS WITH UROTHELIAL CARCINOMA TREATED WITH ENFORTUMAB VEDOTIN WITH PEMBROLIZUMAB (CHEST 2026) - No abstract available

Clinical • Oncology • Pneumonia • Solid Tumor • Urothelial Cancer

Sacituzumab Govitecan (SG) Combined With Enfortumab Vedotin (EV) and Zimberelimab (ZIM) in Treatment-Naive Metastatic Urothelial Cancer (mUC): Interim Results From Phase 1b TROPHY-U-01 Cohort 7 (ESMO 2026) - No abstract available

Metastases • P1 data • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer

Genomic characteristics of patients (pts) with urothelial carcinoma (UC) and early cutaneous toxicity from enfortumab vedotin (EV) plus pembrolizumab (P). (ESMO 2026) - No abstract available

Clinical • Oncology • Solid Tumor • Urothelial Cancer