ESMO Congress 2026

Enfortumab vedotin (EV) is a Nectin-4–directed antibody-drug conjugate (ADC) and pembrolizumab is an anti–PD-1 antibody; the standing of this ADC plus checkpoint inhibitor combination in first-line locally advanced or metastatic urothelial cancer (la/mUC) is anchored by phase III evidence. In EV-302/KEYNOTE-A39, 886 previously untreated la/mUC patients were randomized 1:1 to EV+Pembro versus cisplatin or carboplatin plus gemcitabine, with a median progression-free survival of 12.5 vs 6.3 months (HR 0.450, P<0.0001) and median overall survival of 31.5 vs 16.1 months ^[4]; based on EV-302 and the EV-103 (KEYNOTE-869) Dose Escalation cohort, Cohort A, and Cohort K, the FDA granted traditional approval on December 15, 2023 ^[3][4]. The starting point of the combination was precisely this phase Ib/II EV-103 study: in cisplatin-ineligible previously untreated la/mUC patients, Cohort K showed a confirmed objective response rate of 64.5% for EV+Pembro (N=76) versus 45.2% for EV monotherapy (N=73), with median duration of response not reached for the combination and 13.2 months for monotherapy ^[1].

What was updated at this meeting is the long-term follow-up of EV-103, with follow-up up to 7 years: about 30% of responders were still in response at 7 years; this update, reported by Maroto, was consistent with prior reports — EV+Pembro demonstrated sustained responses and survival with a manageable safety profile. The post also raised next steps: identifying long-term responders through biomarkers (Nectin-4 was mentioned) and optimizing treatment duration with ctDNA.

Relative to existing knowledge, this readout extends the Cohort K combination arm curves — whose median DOR was 'not reached' at the original analysis — out to a 7-year horizon, indicating that responses in a subset of patients can persist for years; more importantly, it moves the clinical question from 'is the combination effective' to 'who will be the long-term benefiters and how long should treatment last', i.e., biomarker-driven patient selection and individualized treatment duration. This shift echoes the context that EV+P is changing the frontline mUC treatment landscape and that clinical questions are moving toward more refined management ^[5].

Limitations: EV-103 is a phase Ib/II study and Cohort K had no formal statistical comparisons between treatment arms ^[1]; the figures in the on-site posts come from a conference presentation, and the definition of responders, arm-level details, and full data are pending confirmation; Nectin-4 and ctDNA are exploratory directions proposed at the meeting rather than validated tools.