Dr Friedlander on the Design and Methods of the Duravelo-2 Trial in Urothelial Cancer

Terence W. Friedlander, MD, genitourinary oncologist, associate clinical professor, Division of Hematology/Oncology, Robert and Virginia O’Reilly Family Endowed Professor of Medicine, University of California San Francisco (UCSF), UCSF Health; chief, Hematology-Oncology, Zuckerberg San Francisco General; associate director, Cancer Research, Helen Diller Family Comprehensive Cancer Center, discusses the design of the phase 2/3 Duravelo-2 study (NCT06225596) of zelenectide pevedotin (BT8009), which is being investigated in the clinical trial in patients with advanced or metastatic urothelial cancer.

Duravelo-2 is an open-label, randomized, global, multicenter trial, Friedlander begins. Cohort 1 will enroll approximately 640 patients. Initially, a 30-patient run-in will assess 2 dosing schedules of zelenectide pevedotin—5 mg/m² vs 6 mg/m²—to determine the optimal dose before transitioning into the phase 3 portion, which will primarily measure progression-free survival, he reports. In the first cohort, the trial will compare frontline zelenectide pevedotin plus pembrolizumab (Keytruda), administered every 3 weeks, against gemcitabine plus cisplatin or carboplatin, he explains. The second cohort will explore zelenectide pevedotin as monotherapy (arms 1 and 2) or in combination with pembrolizumab (arm 3) in patients who have received at least 1 prior systemic therapy. As the study has only recently begun, data on patient accrual and outcomes are expected in the coming months and years, he expands.

Globally, significant challenges to enrollment are not expected, as zelenectide pevedotin offers access to a Nectin-4–targeted antibody-drug conjugate, Friedlander continues. However, in the United States (US), some barriers may arise, particularly due to the randomized nature of the trial’s frontline setting, he explains, noting that the use of gemcitabine plus cisplatin or carboplatin is decreasing in the US.

Nonetheless, data show that patients who receive gemcitabine plus cisplatin or carboplatin followed by avelumab maintenance have median overall survival outcomes comparable with those starting on enfortumab vedotin plus pembrolizumab, according to Friedlander. This could justify enrolling patients on this study, although some patients may prefer immediate treatment with enfortumab vedotin plus pembrolizumab, potentially slowing accrual, Friedlander concludes.