ESMO Congress 2026

Enfortumab vedotin is an antibody-drug conjugate (ADC) targeting Nectin-4, comprising a human anti-Nectin-4 antibody linked to the microtubule-disrupting agent MMAE; Nectin-4 is notably expressed in bladder cancer, with moderate to strong staining seen in 60% of bladder tumor specimens ^[3]. The single-arm phase 2 EV-201 enrolled 125 patients with locally advanced or metastatic urothelial carcinoma progressing after platinum and PD-1/L1 therapy, with a confirmed objective response rate of 44% (95% CI 35.1%–53.2%) and a median follow-up of 10.2 months ^[4]. The phase 3 EV-301 randomized 608 patients 1:1 to enfortumab vedotin or investigator-chosen chemotherapy (docetaxel, paclitaxel, or vinflunine) with overall survival as the primary endpoint; as of July 15, 2020, 134 and 167 deaths had occurred in the enfortumab vedotin and chemotherapy groups, respectively ^[1]. In previously untreated locally advanced or metastatic disease, the phase 3 EV-302 randomized 886 patients to enfortumab vedotin (1.25 mg/kg, days 1 and 8) plus pembrolizumab (200 mg, day 1) versus gemcitabine plus cisplatin or carboplatin (determined by cisplatin eligibility), with progression-free survival by blinded independent central review and overall survival as primary endpoints ^[2].

Two pieces of news emerged at ESMO26. On the regulatory side, per the on-site post, the European Commission has approved pembrolizumab plus enfortumab vedotin as perioperative treatment for adults with resectable muscle-invasive bladder cancer (MIBC), regardless of cisplatin eligibility, which the post called a new therapeutic scenario. On the clinical side, EV-309 was presented: an open-label, randomized phase 3 study of enfortumab vedotin plus pembrolizumab for bladder preservation in patients with MIBC, presented by Matt Galsky of Tisch Cancer. The on-site posts disclosed no efficacy or safety numbers for EV-309, nor any review details attached to the approval decision.

In terms of the evidence map, the phase 3 evidence for the EV combination was previously established in previously untreated advanced urothelial carcinoma (EV-302) ^[2], and single-agent phase 3 evidence in previously treated advanced disease (EV-301) ^[1]. This approval and EV-309 move the same combination into the perioperative setting of resectable MIBC, with the research direction shifting toward bladder preservation, i.e., moving from systemic therapy in advanced disease to intervention around surgery. The approval is not restricted by cisplatin eligibility, in contrast to the EV-302 design in which the chemotherapy arm received cisplatin or carboplatin based on cisplatin eligibility ^[2].

It should be noted that the on-site posts for EV-309 only provided the study design, population, and presenter; sample size, primary endpoint events, bladder preservation success rates, and survival outcomes were not disclosed, so the strength of this interpretation awaits confirmation from the formal written coverage and full data.