The multi-cohort EV-103 study evaluates the safety/activity of enfortumab vedotin + pembrolizumab (Dose Escalation/Cohort A). For this study, Dr. Friedlander highlighted first-line cisplatin-ineligible patients treated with 3-week cycles of enfortumab vedotin 1.25 mg/kg (Days 1, 8) and pembrolizumab (Day 1). Endpoints include safety/tolerability, investigator response per RECIST v1.1, duration of response, progression-free survival, and OS.
As of October 13, 2020, the median follow-up for the 45 first-line locally advanced or metastatic urothelial carcinoma patients was 24.9 months. The median number cycles of enfortumab vedotin + pembrolizumab was 9 (range 1-34). Confirmed objective response rate was 73.3% (95% CI: 58.1, 85.4) including 17.8% complete response and an objective response rate of 57.1% (8/14) in patients with liver metastasis. The best overall response by investigator is as follows, noting 93% of assessable patients had tumor reduction:
The median duration of response was 25.6 months (95% CI: 8.3 to not reached). Fifty-three percent of the responders had duration of response at 24 months. Additionally, the disease control rate is 93.3%, the median progression free survival is 12.3 months (95% CI: 8.0 – not reached), and the median OS is 26.1 months. The OS rate at 24 months is 56.3% (95% CI: 39.8, 69.9):
The most common treatment-related adverse events were peripheral sensory neuropathy (56%, 4% ≥ grade 3), fatigue (51%, 11% ≥ grade 3), and alopecia (49%). There was one death reported as possibly related to study treatment (multiple organ dysfunction syndrome) per investigator assessment.
Dr. Friedlander concluded his presentation of the update EV-103 study with the following conclusions:
- Enfortumab vedotin + pembrolizumab, a platinum-free option, continues to demonstrate promising activity with a durable response profile in first-line cisplatin-ineligible patients with locally advanced or metastatic urothelial carcinoma
- The safety profile is manageable and stable over time with no new safety signals
- Cohort K of EV-103 in cisplatin-ineligible patients with locally advanced or metastatic urothelial carcinoma is actively randomizing patients to enfortumab vedotin monotherapy or enfortumab vedotin + pembrolizumab to evaluate the contribution of each agent
- The phase 3 trial EV-302 is currently enrolling enfortumab vedotin in combination with pembrolizumab versus chemotherapy in patients with locally advanced or metastatic urothelial carcinoma in the first-line setting
Clinical trial information: NCT03288545
Presented by: Terence W. Friedlander, MD, University of California San Francisco Medical Center, San Francisco, CA
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia Twitter: @zklaassen_md at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting, Virtual Annual Meeting #ASCO21, June, 4-8, 2021