Dr. Zhang on the EV-302 Trial in Metastatic Urothelial Cancer

Tian Zhang, MD, associate professor, the Department of Internal Medicine, UT Southwestern Medical Center, discusses the investigation of the combination of enfortumab vedotin-ejfv (Padcev) plus pembrolizumab (Keytruda) in the phase 3 EV-302 trial (NCT04223856) in the frontline setting for metastatic urothelial cancer.

The study is evaluating the combination of enfortumab vedotin and pembrolizumab vs chemotherapy alone in patients with untreated locally advanced or metastatic urothelial cancer.

Several standard-of-care options are currently available for patients with relapsed/refractory urothelial cancer, including the antibody-drug conjugates (ADCs) enfortumab vedotin and sacituzumab govitecan-hziy (Trodelvy), plus the FGFR inhibitor erdafitinib (Balversa) for those with an FGFR3 or FGFR2 alteration.

EV-302 will further examine the potential to utilize enfortumab vedotin in the frontline setting, Zhang says. Previously reported data from the cohort K of the phase 1/2 EV-103 trial (NCT03288545) showed that the combination of the ADC and pembrolizumab elicited a confirmed objective response rate of 64.5% per blinded independent central review, meeting the primary end point of that study.

Safety data showed that the most common grade 3 or higher treatment-emergent adverse effects experienced by more than 5% of patients included maculopapular rash, anemia, increased lipase, urinary tract infection, hyperglycemia, fatigue, neutropenia, hematuria, diarrhea, acute kidney injury, hyponatremia, chronic kidney disease, decreased weight, syncope, hypophosphatemia, pneumonitis, sepsis, and increased alanine aminotransferase.

In December 2022, the FDA granted a priority review to a supplemental biologics license applications for enfortumab vedotin and pembrolizumab used in combination for the treatment of patients with locally advanced or metastatic urothelial cancer who are not eligible to receive cisplatin-containing chemotherapy, based on data from the phase 1/2 trial.

EV-302 will randomly assigned patients in the first-line, metastatic setting to receive enfortumab vedotin with pembrolizumab or standard-of-care gemcitabine and cisplatin chemotherapy. If data from this trial are positive, the combination may replace chemotherapy as the standard-of-care option for patients with metastatic urothelial cancer in the frontline setting, Zhang says.

Accrual for EV-302 is ongoing at various sites, including UT Southwestern Medical Center.