Drs. Gupta, Koshkin on EV-103 Design and Long-term Cohort A Results for Patients With aUC

Shilpa Gupta, MD, Cleveland Clinic, and Vadim Koshkin, MD, University of California, San Francisco, discuss the EV-103 trial and data presented at the 2023 ASCO Annual Meeting, including long-term results for cohort A.

Dr. Koshkin: Let’s begin by discussing the design of EV-103, specifically focusing on cohort A, whose results were presented. What was the main question this cohort sought to investigate?

Dr. Gupta: Sure, EV-103 is an open-label multiple cohort Phase Ib2 study with various cohorts. Cohort A comprised patients with locally advanced or metastatic urothelial cancer who were ineligible for cisplatin. The cohort had a dose escalation portion with 5 patients, followed by a dose expansion with 40 patients. Additionally, there was cohort K, a randomized study comparing EV with pembro versus EV monotherapy, involving 150 cisplatin ineligible treatment-naïve patients. These two cohorts led to the accelerated FDA approval.

Dr. Koshkin: Thank you for the summary. At the recent ASCO conference, you presented updated results from cohort A, which were previously reported a few years back. Could you highlight the main findings from your presentation?

Dr. Gupta: Certainly, in the initial presentation, EV-103 cohort A showed a rapid and durable response with a 68% confirmed objective response rate and a manageable safety profile when combined with cohort K. At ASCO 2023, we presented the median follow-up of 47 months, showing a nearly 4-year follow-up of cohort A. The data continued to demonstrate remarkable activity for this combination.

Dr. Koshkin: Can you provide more insights into the duration of response and other key findings from the updated results?

Dr. Gupta: In the updated results, we observed that patients were treated for a median duration of 7 months with approximately 9 treatment cycles. The duration of response was 22.1 months at this longer follow-up. Notably, at 24 months, 41% of patients remained progression-free, and the median progression-free survival was 12.7 months. The overall survival also exceeded 2 years, at 26.1 months, with an objective response rate of 73.3%.

Dr. Koshkin: This is indeed impressive data with a long follow-up of 4 years. How do these outcomes compare to the standard of care for this patient population before this trial, considering this was a single-arm study?

Dr. Gupta: The standard of care for cisplatin-ineligible patients was based on data from the JAVELIN Bladder 100 trial. It involved gemcitabine and carboplatin for 4 to 6 cycles, followed by maintenance avelumab, which significantly improved overall survival and became the standard in 2020. The updated results from the JAVELIN Bladder 100 trial also show a median overall survival close to 2 years. Comparatively, EV-103’s long-term results are exciting, but we await the results of the EV-302 Phase III trial that compares EV/pembro with platinum-based therapy to gain a clearer picture.

Dr. Koshkin: You made an interesting point about the EV-302 trial, and how it might not provide a clear picture due to the non-standard control arm. Furthermore, your study included all patients, whereas the JAVELIN Bladder 100 population comprised those who responded or had stable disease to carboplatin. Your results, with a median survival of 26 months, compared favorably to historical controls.

View their next discussion on EV-103 Cohort K Results and Toxicities.