The following article features coverage from the 2020 Genitourinary Cancers Symposium meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.

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 ( 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 advanced urothelial carcinoma, 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.

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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 advanced urothelial carcinoma 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 for advanced urothelial carcinoma, EV-302 ( 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.

Read more of our coverage of the 2020 Genitourinary Cancers Symposium by visiting the conference page.


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.