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

EV-302: Exploratory analysis of nectin-4 expression and response to 1L enfortumab vedotin (EV) + pembrolizumab (P) in previously untreated locally advanced or metastatic urothelial cancer (la/mUC) (ESMO 2024) - P3 | "We report the impact of Nectin-4 expression on outcomes with 1L EV+P and chemo. Pts with previously untreated la/mUC were randomized 1:1 to EV (1.25 mg/kg IV; days 1 and 8 Q3W) and P (200 mg IV; day 1 Q3W) or chemo (gemcitabine + cisplatin/carboplatin). EV+P showed consistent PFS and OS benefit across subgroups regardless of Nectin-4 expression. Furthermore, Nectin-4 does not predict for benefit from EV+P."

IO biomarker • Metastases • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer • NECTIN4 • PD-L1

Enfortumab Vedotin Plus Pembrolizumab in Untreated Locally Advanced or Metastatic Urothelial Carcinoma: 2.5-Year Median Follow-Up of the Phase III EV-302/KEYNOTE-A39 Trial. (PubMed, Ann Oncol) - "The continued survival benefit with EV+P compared with chemotherapy at this updated analysis reinforce EV+P as the standard of care for the first-line treatment of patients with la/mUC."

Journal • P3 data • Oncology • Solid Tumor • Urothelial Cancer

Perioperative (periop) enfortumab vedotin (EV) plus pembrolizumab (pembro) in participants (pts) with muscle-invasive bladder cancer (MIBC) who are cisplatin-ineligible: The phase III KEYNOTE-905 study (ESMO 2025) - P3 | "The safety profile of EV + pembro was manageable and consistent with prior reports. This is the first periop regimen to improve outcomes vs RC + PLND in this setting and may be a new standard of care."

Clinical • Late-breaking abstract • P3 data • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor

Phase I study of LY3866288, a potent, highly isoform-selective FGFR3 inhibitor in FGFR3-altered advanced solid tumors (FORAGER-1): Dose optimization (ESMO 2025) - P1 | "Preclinically, LY increases nectin 4 cell surface expression and enhances the antitumor activity of enfortumab vedotin (EV) in FGFR3 -altered mUC in vivo models...LY plus EV and pembrolizumab (EVP) is being studied in 1L mUC (B5)...TEAEs associated with poor tolerance and compliance to erdafitinib were uncommon (PPE 7%, onycholysis 0%, retinopathy 0%)...Cohort B5 opened at 200 mg BID and updated data will be presented. Conclusions LY3866288 at 200 mg BID was well-tolerated and demonstrated promising antitumor activity in FGFRi pretreated and naive pts with FGFR3 -altered mUC, warranting further study as monotherapy and combined with EVP."

Metastases • P1 data • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer • FGFR3 • NECTIN4

KEYMAKER-U04 substudy 04B: First-line (1L) enfortumab vedotin (EV) plus pembrolizumab (pembro)-based immune checkpoint inhibitor (ICI) combinations for advanced urothelial cancer (UC). (ASCO-GU 2026) - P1/2 | "Clinical Trial Registry Number: NCT05845814. The full, final text of this abstract will be available on Feb 23 at 05:00 PM EST."

Checkpoint inhibition • Clinical • Metastases • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer

Neoadjuvant and adjuvant enfortumab vedotin (EV) plus pembrolizumab (pembro) for participants with muscle-invasive bladder cancer (MIBC) who are eligible for cisplatin: Randomized, open-label, phase 3 KEYNOTE-B15 study. (ASCO-GU 2026) - P3 | "Clinical Trial Registry Number: NCT04700124. The full, final text of this abstract will be available on Feb 27 at 10:00 AM EST."

Clinical • Late-breaking abstract • P3 data • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor

Pathological outcomes and disease-free survival (DFS) in KEYNOTE-905: Neoadjuvant and adjuvant (neoadj-adj) enfortumab vedotin (EV) plus pembrolizumab (pembro) in participants (pts) with muscle-invasive bladder cancer (MIBC) who are cisplatin-ineligible. (ASCO-GU 2026) - P3 | "Clinical Trial Registry Number: NCT03924895. The full, final text of this abstract will be available on Feb 23 at 05:00 PM EST."

Clinical • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor

FGFR Testing in Metastatic Urothelial Carcinoma-Who, When, and How to Test. (PubMed, Cancers (Basel)) - "This has broadened the treatment landscape of the disease to include novel agents, such as antibody-drug conjugates (e.g., enfortumab vedotin) and targeted therapies, including the pan-fibroblast growth factor receptor (FGFR) inhibitor erdafitinib. Equally important is the standardization and timely implementation of FGFR3 testing in clinical practice to optimize treatment planning. This review addresses key considerations in FGFR3 testing in mUC and discusses how it can be routinely incorporated into clinical practice."

Journal • Review • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer • FGFR • FGFR3

Neoadjuvant and adjuvant enfortumab vedotin (EV) plus pembrolizumab (pembro) for participants with muscle-invasive bladder cancer (MIBC) who are eligible for cisplatin: Pathological and surgical outcomes in KEYNOTE-B15 (EAU 2026) - No abstract available

Clinical • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor

Pre-treatment Dexamethasone to Prevent Cutaneous Toxicity During First-line Enfortumab Vedotin plus Pembrolizumab: A Multicenter Prospective Study (EAU 2026) - No abstract available

Clinical • Oncology • Solid Tumor • Urothelial Cancer

ENCORE: Enfortumab Vedotin as Monotherapy in Patients With Metastatic Castration-Resistant Prostate Cancer (clinicaltrials.gov) - P2 | N=34 | Active, not recruiting | Sponsor: University of Utah | Trial primary completion date: Jan 2026 ➔ Apr 2025

Monotherapy • Trial primary completion date • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Solid Tumor

Poorly differentiated neuroendocrine transformation from metastatic upper tract urothelial carcinoma. (PubMed, BMJ Case Rep) - "This report presents the first documented case of metastatic urothelial carcinoma transforming into neuroendocrine carcinoma, potentially as a resistance mechanism to enfortumab-vedotin therapy, as the dynamic nature of tumour cells may contribute to resistance against evolving microenvironments and novel interventions. In this context, performing biopsies during disease progression serves as a critical tool for elucidating tumour plasticity and enhancing therapeutic strategies."

Journal • Endocrine Cancer • Genito-urinary Cancer • Genitourinary Neuroendocrine Carcinoma • Neuroendocrine Carcinoma • Oncology • Solid Tumor • Urethral Cancer • Urothelial Cancer

Deep early tumour shrinkage in metastatic upper tract urothelial carcinoma treated with enfortumab vedotin plus pembrolizumab. (PubMed, BJU Int) - No abstract available

Journal • 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

Real-Life Impact of Enfortumab Vedotin or Chemotherapy in the Sequential Treatment of Advanced Urothelial Carcinoma: The ARON-2 Retrospective Experience. (PubMed, Cancer Med) - P | "The results of our international analysis of real-world data confirm the effectiveness of EV in the sequential strategy of aUC patients who have received prior platinum-based chemotherapy and anti-PD-1 pembrolizumab, regardless of commonly considered prognostic factors."

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

CLONEVO: Preoperative abemaciclib for cisplatin-ineligible muscle-invasive bladder cancer (MIBC) with molecular response assessment. (ASCO 2025) - P1 | "Funded by Eli Lilly Clinical Trial Registration Number: NCT03837821 Background: Up to 40% of MIBC patients are ineligible to receive standard neoadjuvant cisplatin-based chemotherapy creating a significant unmet need. This first trial of short-term preoperative abema in MIBC demonstrated promising efficacy and tolerability while modulating cell cycle-dependent pathways. Our findings support future trials investigating sequential abema with antibody-drug conjugates such as enfortumab vedotin, where abema's effects on DSBs repair augment treatment response."

Anemia • Bladder Cancer • Genito-urinary Cancer • Oncology • Pain • Solid Tumor • CCNA2 • CCND1 • HRD • PCNA • RAD51 • RB1 • TOPBP1

Pre-operative abemaciclib in localized cisplatin-ineligible MIBC with tissue and ctDNA molecular response validation (CLONEVO) (AACR 2025) - P1 | "Background: Up to 40% of patients with muscle-invasive bladder cancer (MIBC) are ineligible to receive standard-of-care neoadjuvant cisplatin-based chemotherapy, creating a significant unmet need for effective neoadjuvant therapies. This first trial of short-term pre-operative abema in MIBC demonstrated favorable efficacy and tolerability while modulating cell cycle-dependent pathways, including DSB repair. Our findings support future trials investigating sequential therapy combining abema with antibody-drug conjugates such as enfortumab vedotin, where abema's effects on DSB repair enhance treatment responses."

Circulating tumor DNA • Bladder Cancer • Oncology • CCNA2 • CCND1 • MKI67 • PCNA • RAD51 • TOPBP1

CONSOLIDATE-01: PHASE II TRIAL OF CONSOLIDATIVE SURGERY FOLLOWING ENFORTUMAB VEDOTIN AND PEMBROLIZUMAB IN PATIENTS WITH LOCALLY ADVANCED/OLIGOMETASTATIC UROTHELIAL CARCINOMA (SUO 2025) - P2 | "Trial registration: NCT07048457. "

Clinical • Metastases • P2 data • Surgery • Oncology • Solid Tumor • Urothelial Cancer

Merck Advances Treatment of Bladder and Kidney Cancers with New Data at 2026 ASCO GU Cancers Symposium (Businesswire) - "Late-breaking KEYNOTE-B15 data show KEYTRUDA (pembrolizumab) plus Padcev (enfortumab vedotin-ejfv) significantly improved event-free survival, overall survival and pathologic complete response rates for patients with certain types of bladder cancer; New LITESPARK-022 and LITESPARK-011 data highlight the disease-free survival benefit of WELIREG (belzutifan) plus KEYTRUDA and progression-free survival benefit of WELIREG in combination with LENVIMA (lenvatinib), respectively; Sacituzumab tirumotecan (sac-TMT) plus pembrolizumab (pembro) in participants (Pts) with advanced urothelial carcinoma (UC): Results from the Phase 2 2870-002/SKB264-II-06 study; Efficacy and safety of the DLL3 T-cell engager gocatamig in participants (pts) with neuroendocrine prostate cancer (NEPC) and other neuroendocrine neoplasms (NEN)"

Clinical data • Bladder Cancer • Clear Cell Renal Cell Carcinoma • Genitourinary Neuroendocrine Carcinoma • Neuroendocrine Neoplasm • Urothelial Cancer

Exploratory analysis of responders from the phase 3 EV-302 trial of enfortumab vedotin plus pembrolizumab (EV+P) vs chemotherapy (chemo) in previously untreated locally advanced or metastatic urothelial carcinoma (la/mUC). (ASCO 2025) - P3 | " Pts were randomized 1:1 to receive EV (1.25 mg/kg; Days 1 and 8; IV) + P (200 mg; Day 1; IV) or chemo (gemcitabine + cisplatin/carboplatin); all Q3W. In the EV+P arm, the proportion of pts achieving cCR was twice that in the chemo arm. Consistent with the ITT data, EV+P reduced the risk of progression or death vs chemo in pts achieving cCR, with appropriate dose modifications. These data reinforce EV+P as the SOC for 1L tx of pts with la/mUC."

Metastases • P3 data • Oncology • Solid Tumor • Urothelial Cancer

Enfortumab vedotin plus pembrolizumab versus chemotherapy in patients with previously untreated locally advanced or metastatic urothelial cancer (EV-302): patient-reported outcomes from an open-label, randomised, controlled, phase 3 study. (PubMed, Lancet Oncol) - P3 | "Enfortumab vedotin plus pembrolizumab significantly improved survival outcomes versus platinum-based chemotherapy without detriment to GHS/QOL, pain, or functioning. Patients with moderate to severe baseline pain had clinically meaningful improvements in worst pain and GHS/QOL with enfortumab vedotin plus pembrolizumab. These data provide further evidence to support the use of enfortumab vedotin plus pembrolizumab as a preferred treatment option for patients with previously untreated locally advanced or metastatic urothelial cancer."

Clinical • IO biomarker • Journal • P3 data • Genito-urinary Cancer • Oncology • Pain • Solid Tumor • Urothelial Cancer • PD-L1

Target-dependent in-vitro efficacy of Sacituzumab govitecan and Enfortumab vedotin in penile cancer (DKK 2026) - No abstract available

Preclinical • Genito-urinary Cancer • Oncology • Penile Cancer • Solid Tumor

Case presentation 2: Tumor progression after first-line therapy with enfortumab vedotin and pembrolizumab (DKK 2026) - No abstract available

Clinical • Oncology

NECTIN-4 as a Novel Therapeutic Target in Sinonasal Undifferentiated Carcinoma: Durable Response to Enfortumab Vedotin in a Biomarker-Selected Case (DKK 2026) - No abstract available

Biomarker • Clinical • Oncology • NECTIN4

Treatment Sequencing in Advanced Urothelial Cancer. (PubMed, Drugs) - "Accordingly, gemcitabine-cisplatin with nivolumab and platinum-based chemotherapy followed by maintenance avelumab remain validated evidence-based alternatives, particularly for cisplatin-eligible patients or in regions where enfortumab vedotin plus pembrolizumab is not readily accessible...Enfortumab vedotin monotherapy retains activity post-platinum and immune checkpoint inhibition, erdafitinib provides a targeted benefit in fibroblast growth factor receptor 3-altered tumors, and trastuzumab deruxtecan has emerged as a later-line option for HER2-positive disease. In parallel, circulating tumor DNA is an emerging biomarker with potential to individualize sequencing strategies, although its clinical application remains investigational. This review synthesizes current evidence and highlights practical considerations, emphasizing the need to balance therapeutic innovation with cost effectiveness, equitable access, and global applicability, while identifying critical..."

IO biomarker • Journal • Review • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer • FGFR3 • HER-2