Trial Results Find Enfortumab Vedotin-ejfv, Pembrolizumab Combination Effective in Urothelial Cancer


The combined enfortumab vedotin-ejfv and pembrolizumab treatment is recommended for patients with locally advanced or metastatic urothelial cancer who are ineligible for cisplatin-containing therapy.

Topline results from the phase 3 EV-302 clinical trial for a combined treatment of enfortumab vedotin-ejfv (Padvec; Agensy, Inc. and Seagen, Inc.) and pembrolizumab (Keytruda; Merck) were recently announced. The combination treatment was compared with chemotherapy in patients with previously untreated locally advanced or metastatic urothelial cancer (la/mUC), a form of bladder cancer that spreads to neighboring organs, muscles, or other parts of the body.

Enfortumab vedotin is an antibody-drug conjugate that is directed against nectin-4, a protein found on cell surfaces that are prominent in bladder cancer. It is a treatment indicated for adult patients with la/mUC who have previously received a programmed death receptor-1 or programmed death-ligand 1 (PD-L1) inhibitor and platinum-containing chemotherapy, or if they are ineligible for cisplatin-containing chemotherapy and have previously received 1 or more prior methods of therapy.

Detail of high grade urothelial carcinoma of the ureter in a man. The tumor has central necrosis which appears pink. Microscopic view.

Image credit: Lisa -

The combined therapy of enfortumab vedotin and pembrolizumab is indicated for the treatment of adult patients with la/mUC who are ineligible for cisplatin-containing therapy. Currently, this indication is approved under accelerated approval based on the tumor’s response rate and durability of response; however, continued approval may be dependent on the verification of clinical benefit in confirmatory research.

The EV-302 trial is an open-label, randomized, controlled phase 3 study that evaluated the efficacy of combined therapy of enfortuman vedotin and pembrolizumab compared to chemotherapy in patients with previously untreated la/mUC. Enrolled patients were randomized to receive either enfortumab vedotin in combination with pembrolizumab, or chemotherapy.

"We are thrilled that the topline results of the EV-302 study demonstrated that the combination of enfortumab vedotin and pembrolizumab improved the dual primary endpoints of [overall survival] and [progression-free survival],” Ahsan Arozullah, MD, MPH, Astellas senior vice president and head of oncology development, said in a press release. “Patients living with metastatic urothelial cancer are in dire need of additional treatment options and this combination has the potential to advance the standard of care. We are extremely grateful to all of the patients who participated in this trial."

The EV-302 trial had enrolled patients with previously untreated la/mUC who were eligible for cisplatin- or carboplatin-containing chemotherapy, regardless of their PD-L1 status. The study had met both primary endpoints of overall survival (OS) and progression-free survival (PFS), compared to chemotherapy. Further, the safety results of the enfortumab vedotin and pembrolizumab combination therapy is consistent with previously reported patients with cisplatin who were ineligible for la/mUC.

"This study has the potential to be practice changing and offer a new standard of care for first-line metastatic bladder cancer. We look forward to presenting the results at an upcoming medical conference and discussing with regulators in order to get this medicine to patients as soon as possible,” said Roger Dansey, MD, president of research and development at Seagen, in the press release.

Potential adverse effects (AEs) when receiving treatment with enfortumab vedotin-ejfv include skin reactions, hyperglycemia and diabetic ketoacidosis, pneumonitis or interstitial lung disease, peripheral neuropathy, ocular complications, extravasation at infusion site, and embryo-fetal toxicity for individuals who are pregnant. The most common AEs reported were rash, fatigue, decreased appetite, diarrhea, nausea, reductions in weight, and dry skin.

"Over 200,000 deaths from urothelial cancer are reported worldwide annually, making it a major cause of morbidity and mortality,” said EV-302 primary investigator Thomas Powles, MRCP, MD, professor of genitourinary oncology at Queen Mark University of London and director of Barts Cancer Center, London, in a press release. “The topline results from EV-302 are encouraging for patients with advanced-stage urothelial cancer, which is aggressive and associated with devastating outcomes.”


Seagen. PADCEV® (enfortumab vedotin-ejfv) and KEYTRUDA® (pembrolizumab) Significantly Improve Overall Survival and Progression-Free Survival in Patients With Previously Untreated Advanced Bladder Cancer in Pivotal Phase 3 EV-302 Trial. News release. September 22, 2023. Accessed September 25, 2023.

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