EV-103 Cohort K: Promising data for first-line combination therapy of enfortumab vedotin plus pembrolizumab for patients with urothelial carcinoma

EV-103 (NCT03288545) is a multicohort study investigating the use of the antibody-drug conjugate, enfortumab vedotin, alone or in combination with other therapies for patients with urothelial carcinoma (UC)¹. There is a need for tolerable first-line treatment options in metastatic or locally advanced urothelial carcinoma, for which enfortumab vedotin could be a potential solution.

Results from Cohort K were presented at the European Society for Medical Oncology (ESMO) 2022 Annual Meeting in Paris, France². The aim of this arm of the trial was to investigate the antitumor activity of enfortumab vedotin monotherapy versus the combination therapy of enfortumab vedotin plus pembrolizumab, in the first-line setting for cisplatin-ineligible patients with locally advanced or metastatic UC.

149 patients were included in Cohort K, with 73 receiving enfortumab vedotin monotherapy and 76 receiving combination therapy². Patients who received the monotherapy were treated with enfortumab vedotin on day 1 and day 8 in a 21-day cycle. Patients who received the combination therapy were treated with the same schedule of enfortumab vedotin with the addition of pembrolizumab on day 1. The primary outcome for this cohort was confirmed objective response rate (ORR) (via blinded independent central review using RECIST 1.1)¹.

The monotherapy group achieved a confirmed OOR 45.2%, with a median duration of response of 13.2 months. The combination therapy group achieved a confirmed ORR of 64.5%, with the median duration of response not reached. Treatment-related adverse events among both groups included skin reactions, peripheral neuropathy, ocular disorders, and hyperglycaemia. Most of these events were grade 2 or below².

We spoke to Dr Jonathan Rosenberg, MD, from Memorial Sloan Kettering Cancer Center, New York, NY, about these results at ESMO 2022:

In conclusion, the combination therapy of enfortumab vedotin plus pembrolizumab reported a high ORR and was well-tolerated, making it a promising future first-line option for cisplatin-ineligible patients with locally advanced or metastatic urothelial carcinoma.

References:

1. A Study of Enfortumab Vedotin Alone or With Other Therapies for Treatment of Urothelial Cancer – Full Text View – ClinicalTrials.gov [Internet]. Clinicaltrials.gov. 2022 [cited 27 September 2022]. Available from: https://clinicaltrials.gov/ct2/show/NCT03288545
2. Rosenberg J, Milowsky M, Ramamurthy C, et al. LBA73 Study EV-103 Cohort K: Antitumor activity of enfortumab vedotin (EV) monotherapy or in combination with pembrolizumab (P) in previously untreated cisplatin-ineligible patients (pts) with locally advanced or metastatic urothelial cancer (la/mUC). Annals of Oncology [Internet]. 2022;33:S1441. Available from: https://oncologypro.esmo.org/meeting-resources/esmo-congress/study-ev-103-cohort-k-antitumor-activity-of-enfortumab-vedotin-ev-monotherapy-or-in-combination-with-pembrolizumab-p-in-previously-untreated-c

Written by Helena Gibbon