Dr Friedlander on the Duravelo-2 Trial for Advanced or Metastatic 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 investigation of zelenectide pevedotin (BT8009) in the phase 2/3 Duravelo-2 study (NCT06225596) in patients with advanced or metastatic urothelial cancer.

One study that aims to enhance existing effective therapies for patients with urothelial cancer isDuravelo-2, for which Friedlander is an investigator. This study examines the peptide-drug conjugate zelenectide pevedotin, which may have similar activity to enfortumab vedotin-ejfv (Padcev) but is potentially associated with less toxicity, he begins. The smaller size of the zelenectide pevedotin molecule could allow it to penetrate the tumor microenvironment more effectively, potentially resulting in better drug activity and reduced persistence in circulation, he reports. This smaller size may lead to fewer lingering toxic effects, especially skin toxicity, as indicated by initial phase 1/2 trial (NCT04561362) data in patients with Nectin-4–expressing advanced malignancies, Friedlander explains.

Although developing universally effective therapies takes time, improving upon existing ones is valuable, he says, noting that patients with urothelial cancer may also benefit from receiving these therapies earlier in the disease course. Currently, research is focused on locally advanced and metastatic disease, but agents such as PD-1 inhibitors are moving into the perioperative setting to help prevent relapse after bladder removal, he continues.

Important studies have also been conducted in the neoadjuvant setting, where therapy is given without bladder removal, Friedlander states. One such study, the phase 2 HCRN GU 16-257 trial (NCT03558087), involved patients with muscle-invasive bladder cancer who received neoadjuvant nivolumab (Opdivo) plus platinum-based chemotherapy. Patients with a complete clinical response were allowed to keep their bladders, and most did not experience metastatic relapse, he reports.

The ability to avoid cystectomy would be a significant achievement for the bladder cancer treatment field, Friedlander expands. Improving frontline therapies in metastatic cases and developing novel therapies for later-line treatment are also crucial, he says. Additionally, radiation therapy for bladder cancer is being studied in combination with PD-1 inhibitors or enfortumab vedotin as a form of bladder preservation, according to Friedlander. These studies offer promising new treatment approaches, and their outcomes are highly anticipated, Friedlander concludes.