Dr Shore on the Rationale for the Duravelo-2 Trial in Metastatic Urothelial Cancer

Neal D. Shore, MD, FACS, medical director, Carolina Urologic Research Center, Atlantic Urology Clinics, discusses early data from the phase 1/2 Duravelo-1 trial (NCT04561362) investigating zelenectide pevedotin (formerly BT8009) in patients with metastatic urothelial carcinoma. He also highlights the rationale for the ongoing phase 2/3 Duravelo-2 trial (NCT06225596).

In the Duravelo-1 trial, this first-in-class agent, known as a bicycle toxin conjugate, showed efficacy as monotherapy in patients who had not received prior treatment with enfortumab vedotin-ejfv (Padcev). Currently, the Duravelo-2 trial is enrolling patients with locally advanced or metastatic urothelial cancer and will evaluate zelenectide pevedotin as both monotherapy and in combination with pembrolizumab (Keytruda) across different dose levels.

Earlier-phase studies highlighted promising efficacy outcomes, including durable objective response rates with the agent, leading to the development of the Duravelo-2 study, Shore begins. Shore states that his institution was honored to be the first site to enroll a patient to this trial and that enrollment has been progressing well among patients with locally advanced or metastatic urothelial cancer. This study includes 2 cohorts: previously untreated patients and patients who have undergone prior treatment, he reports. Patients in both groups receive treatment with zelenectide pevedotin at doses of 5 mg/m² or 6 mg/m², Shore states, noting that investigators are eager to observe response rates and assess efficacy across dose levels.

According to Shore, an important aspect of advancing bladder cancer research involves examining previous study results, such as those from the randomized, open-label, phase 3 EV-302 trial (NCT04223856), which led to the FDA approval of enfortumab vedotin plus pembrolizumab for the treatment of patients with locally advanced or metastatic urothelial cancer. Another notable trial is the phase 3 CheckMate 901 study (NCT03036098), which combined nivolumab (Opdivo) with cisplatin and gemcitabine in patients with treatment-naive, inoperable or metastatic urothelial cancer, Shore reports. Investigators are also focused on understanding the role of maintenance therapy with avelumab (Bavencio) in the context of new trial data, as guided by prior findings from the phase 3 JAVELIN Bladder 100 trial (NCT02603432) in patients with advanced urothelial carcinoma who were progression free after frontline chemotherapy, he continues. More data on maintenance therapy strategies and their effects on outcomes are anticipated, Shore adds.

Ultimately, although other targets and treatments are being explored, the Duravelo-2 trial of zelenectide pevedotin remains a current focus in the bladder cancer field, he expands. This trial may provide patients with an additional treatment option and generate deeper insights into managing advanced urothelial cancers, especially with maintenance therapies and targeted drug conjugates, Shore concludes.