(UroToday.com) The 2023 American Society of Clinical Oncology Genitourinary (ASCO GU) cancers symposium held in San Francisco, CA between February 16th and 18th was host to a urothelial carcinoma trials in progress poster session. Dr. Ashish Kamat presented the study design for EV-104, a phase 1 study of intravesical enfortumab vedotin for the treatment of patients with non-muscle invasive bladder cancer (NMIBC).
Dr. Kamat began by noting that approximately 75% of patients with bladder cancer present with non-muscle invasive bladder cancer (NMIBC). The current paradigm for high-risk NMIBC involves transurethral resection of the bladder tumor (TURBT) followed by intravesical Bacillus Calmette-Guerin (BCG) or chemotherapy. Although initial response rates to BCG therapy are high, many patients recur within 1-5 years. Options for patients with BCG unresponsive disease remain limited at the current time. While radical cystectomy is still considered standard of care in this setting, many patients are either unwilling or unfit to undergo radical surgery. As such, current options are mainly limited to intravesical chemotherapy or pembrolizumab.1
Enfortumab vedotin (EV) is Nectin-4 targeted antibody-drug conjugate. Nectin-4 is highly expressed on bladder tumor cells, making it an attractive target for such agents. Systemic use of EV has previously demonstrated an overall survival benefit in the 3rd line setting for patients with locally advanced or metastatic urothelial carcinoma, who had previously received platinum-based therapy and a PD-1 or PD-L1 inhibitor (EV-301).2 Based on its demonstrated benefit in locally advanced/metastatic urothelial carcinoma, EV is currently being evaluated in earlier settings, such as in the neoadjuvant setting. The objective of this study is to investigate the intravesical administration of EV for patients with NMIBC.
EV-104 (NCT05014139) is a phase 1, open-label, multicenter, dose-escalation, and dose-expansion study of intravesical EV in adults with high-risk BCG-unresponsive NMIBC (CIS +/- papillary disease) who are ineligible for or refuse radical cystectomy. The study endpoints are as follows:
The dose escalation part of the trial aims to identify the maximum tolerated dose (MTD) and/or recommended dose of intravesical EV. To identify the recommended dose, escalation rules will be guided by the modified toxicity probability interval design using a Bayesian model for “escalation”, “stay”, or “de-escalation” in approximately 18 patients. Subsequently, the dose expansion part will evaluate patients at the MTD or recommended dose and further characterize safety and antitumor activity of intravesical EV (up to 2 dose expansion cohorts of up to 40 patients).
Similar in concept to BCG and intravesical chemotherapy regimens, the EV-104 treatment regimen will include an induction phase, whereby patients will receive intravesical EV weekly for 6 weeks followed by monthly maintenance for a total of 9 additional EV doses.
Patients will undergo mandatory 3-month assessments via cystoscopy and urine cytology while on study. Annual upper tract imaging will be performed as clinically indicated during treatment. Bladder mapping biopsies will be performed at 12 months. Surveillance and recording of AEs, SAEs, recording of concomitant medications, and measurements of protocol-specified physical examination findings and laboratory tests will be recorded.
The study is currently enrolling in the United States (since January 2022) with additional sites planned in Canada and Europe, including the UK (Clinical trial information: NCT05014139)
Presented by: Ashish M. Kamat, MD, MBBS, Endowed Professor of Urologic Oncology (Surgery) and Cancer Research, Department of Urology, University of Texas MD Anderson Cancer Center, Houston, TX
Written by: Rashid Sayyid, MD, MSc – Society of Urologic Oncology (SUO) Clinical Fellow at The University of Toronto, @rksayyid on Twitter during the 2023 Genitourinary (GU) American Society of Clinical Oncology (ASCO) Annual Meeting, San Francisco, Thurs, Feb 16 – Sat, Feb 18, 2023.
References:
- Balar AV, et al. Pembrolizumab monotherapy for the treatment of high-risk non-muscle-invasive bladder cancer unresponsive to BCG (KEYNOTE-057): an open-label, single-arm, multicentre, phase 2 study. Lancet Oncol 2021;22(7):919-930.
- Powles T, et al. Enfortumab Vedotin in Previously Treated Advanced Urothelial Carcinoma. N Engl J Med 2021;384:1125-1135.