(UroToday.com) The 2026 GU ASCO annual meeting featured a urothelial carcinoma trials in progress session and a presentation by Dr. Vadim Koshkin discussing EV-PRIME, a phase Ib/II study of enfortumab vedotin and pembrolizumab combined with radiotherapy as a bladder-sparing trimodality therapy in muscle-invasive bladder cancer.
The enfortumab vedotin and pembrolizumab combination is highly effective for patients with metastatic urothelial cancer, with a response rate of 68% that includes many durable responses.1 This combination has also demonstrated activity in the perioperative setting for patients with muscle-invasive bladder cancer, based on results of the KEYNOTE-905/EV-303 trial. Current standard of care treatment for patients with muscle invasive bladder cancer remains systemic therapy followed by radical cystectomy. However, for selected patients who are either not radical cystectomy candidates or prefer a bladder-sparing approach, trimodality therapy with TURBT followed by combined chemotherapy and radiation therapy constitutes an alternative treatment option. The efficacy and durable responses observed with enfortumab vedotin/pembrolizumab support the rationale of combining this regimen with radiation therapy for patients with muscle-invasive bladder cancer, allowing patients to potentially forego extensive surgery.
This is a phase Ib/II, multi-center, investigator-initiated trial of bladder sparing tri-modality therapy in muscle invasive bladder cancer, utilizing enfortumab vedotin and pembrolizumab in combination with standard fractionation bladder radiation therapy following TURBT (within 8 weeks of treatment start). Eligible patients have biopsy-confirmed muscle-invasive bladder cancer (cT2-T4a) with a component of urothelial histology, but no evidence of metastatic disease on imaging (M0), and have an ECOG performance status ≤1. Patients will be either ineligible for radical cystectomy or declining surgery and will not have contraindications to receiving either enfortumab vedotin or pembrolizumab. Enrolled patients will receive 2 cycles (6 weeks) of treatment with a combination of enfortumab vedotin and pembrolizumab and concurrent conventionally fractionated radiation therapy (64Gy/32Fx), followed by adjuvant enfortumab vedotin for 3 cycles (5 total cycles maximum) and pembrolizumab for 15 cycles (17 total cycles maximum). The trial will start with a phase Ib 3+3 dose escalation of enfortumab vedotin at three dose levels (0.75 mg/kg, 1.00 mg/kg, 1.25 mg/kg) given on Days 1,8 of a 21-day cycle, in combination with standard dose of pembrolizumab 200 mg IV (Day 1 of 21-day cycle) and radiation therapy, to define the safety of this combination and determine the recommended phase II dose of enfortumab vedotin as part of this regimen. In the phase II portion of the study, patients will be treated at the recommended phase II dose of enfortumab vedotin in combination with a standard dose of pembrolizumab and radiation therapy, to assess the efficacy of this combination:
The primary efficacy endpoint is the 6-month clinical complete response in the phase II portion of the study. Important secondary endpoints include median recurrence-free survival, median cystectomy-free survival, and median overall survival. The study is open and currently actively accruing patients in phase Ib dose escalation at UCSF. This trial will aim to enroll 35 patients at the recommended phase II dose, and up to 47 patients total at 3 high-volume centers. Clinical trial information NCT06470282.
Presented by: Vadim S. Koshkin, MD, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Wellstar MCG Health, @zklaassen_md on Twitter during the 2026 Genitourinary (GU) American Society of Clinical Oncology (ASCO) Annual Meeting, San Francisco, CA, Thurs, Feb 26 – Sat, Feb 28, 2026.
Related content: EV-PRIME Assesses Safety and Efficacy of Combined Systemic and Local Therapy in MIBC - Raj Satkunasivam
EV-PRIME: Enfortumab Vedotin and Pembrolizumab with Radiation in Patients Declining Cystectomy - Vadim Koshkin
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