Dr Bilusic on the Investigation of Enfortumab Vedotin in Rare GU Cancers

Marijo Bilusic, MD, PhD, GU site disease group lead, GU SDD medical oncology lead, University of Miami Miller School of Medicine, Sylvester Comprehensive Cancer Center, discusses the rationale for investigating enfortumab vedotin-ejfv (Padcev) with or without pembrolizumab (Keytruda) in patients with rare genitourinary (GU) tumors in the phase 2 E-VIRTUE study (NCT06041503).

Notably, information on the multicenter study was presented at the 2024 ASCO Annual Meeting. E-VIRTUE is an open-label, nonrandomized study that is evaluating patients with locally advanced or metastatic urinary tract pure adenocarcinoma, urinary tract pure squamous cell carcinoma (SCC), or refractory germ cell tumors with measurable disease per RECIST v1.1 criteria. The primary objective of the study is to assess objective response rate across all cohorts. Secondary objectives include safety, progression-free survival, and overall survival.

Bilusic begins by stating that there is a strong rationale for conducting this research in the population of patients with rare GU cancer histologies that is being enrolled, as this population currently has no standard of care. This investigation builds on preclinical work showing that NECTIN-4 is overexpressed in most patients with bladder adenocarcinoma, bladder SCC, and testicular cancer, he emphasizes. Therefore, there is a hypothesis that NECTIN-4 could be a potential target for antibody-drug conjugates, Bilusic explains.

The trial is enrolling patients with these rare histologies, including those who may have previously received checkpoint inhibitors, Bilusic continues. Patients will be divided into 2 cohorts. One cohort will consist of checkpoint inhibitor–naïve patients who will receive the combination of enfortumab vedotin and pembrolizumab on a standard schedule that is FDA approved for locally advanced or metastatic urothelial cancer. The second cohort will include patients who have progressed on checkpoint inhibitors and will receive enfortumab vedotin monotherapy, also on a standard schedule, he reports. Patients will continue enfortumab vedotin treatment for up to 5 years andpembrolizumab treatment for up to 2 years. Patients in the combination arm who achieve complete responses can stop pembrolizumab but may resume it if they experience disease progression in the future, Bilusic concludes.