A new combination therapy for advanced urothelial carcinoma (UC) demonstrated promising early results, which were presented at the 2020 Genitourinary Cancers Symposium in San Francisco, California. These results featured the phase 1/2 trial results (ClinicalTrials.gov Identifier: NCT03288545) from a combination of pembrolizumab and enfortumab vedotin (EV). EV is an antibody-drug conjugate carrying a payload of the microtubule inhibitor monomethyl auristatin E (MMAE). The antibody is targeted to Nectin-4, a protein highly expressed in UCs. Both EV and pembrolizumab have individually shown some efficacy in UC, but this trial is investigating the combination.

Forty-five patients, ineligible for standard first-line therapy of platinum agents, were treated with the new combination, with approximately 73% achieving an overall response, and approximately 93% seeing at least some reduction in tumor size. The median progression-free survival was 12.3 months and the trial posted an 81.6% (95% CI, 62.0-91.8) overall survival rate at 12 months; the median OS had not yet been reached.

The study also measured PD-L1 status of the patients, with no correlation seen between PD-L1 expression and response to treatment. With regard to the toxicity profile of the combination, there were 7 patients (16%) reporting treatment-related adverse events, 6 of which resolved. There was 1 treatment-related death reported (multiple organ dysfunction syndrome). Six patients discontinued the combination treatment due to toxicity. Of 45 individuals,13 experienced immune-mediated adverse events of any grade requiring systemic steroids, and 8 of these participants experienced grade 3 or higher immune-mediated adverse events requiring steroids.

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An upcoming phase 3 trial, EV-302 (ClinicalTrials.gov Identifier: NCT4223856), will evaluate enfortumab vedotin in combination with pembrolizumab with or without chemotherapy compared with the standard of care gemcitabine-platinum in patients with la/mUC in the first-line setting. It aims to enroll over 1000 patients, and the trial is expected to begin recruitment later this month.

Disclosure: This research was funded by Seattle Genetics. For a full list of disclosures, please refer to the meeting abstract.


Rosenberg JE, Flaig TW, Friedlander TW, et al. Study EV-103: Preliminary durability results of enfortumab vedotin plus pembrolizumab for locally advanced or metastatic urothelial carcinoma. Presented at: 2020 Genitourinary Cancers Symposium; February 13-15, 2020; San Francisco, CA. Abstract 441.

This article originally appeared on Cancer Therapy Advisor