Phase 2 Trial Sees Positive Topline Results with Enfortumab Vedotin-ejfv in Advanced Urothelial Cancer

October 12, 2020

“This is the first trial to report objective responses in patients with advanced urothelial cancer who had previously received immunotherapy but were ineligible for cisplatin in this setting due to inadequate kidney function or other conditions,” Roger Dansey, MD, said in a press release.

Positive topline results from the second cohort of patients in the single-arm, pivotal, phase 2 EV-201 clinical trial, evaluating the antibody-drug conjugate (ADC) enfortumab vedotin-ejfv (Padcev) for patients with locally advanced or metastatic urothelial cancer who have been previously treated with a PD-1 or PD-L1 inhibitor and have not received a platinum-containing chemotherapy and are ineligible for cisplatin, were announced by Seagen and Astellas Pharma, the co-developers of the agent.

Results from the trial demonstrated a 52% objective response rate (ORR) (95% CI, 40.8-62.4) per blinded independent central review and a median duration of response of 10.9 months. Regarding safety, the most frequently reported treatment-related adverse events (AEs) of grade 3 or greater that occurred in more than 5% of patients were neutropenia, rash, fatigue, increased lipase, diarrhea, decreased appetite, anemia, and hyperglycemia.

Data from cohort 2 of the EV-201 trial will be submitted for presentation at an upcoming scientific congress and will be discussed with regulatory authorities.

“Advanced urothelial cancer in patients who have received immunotherapy and are ineligible for cisplatin is a particularly difficult disease to treat,” Arjun V. Balar, MD, director of the genitourinary medical oncology program at NYU Langone’s Perlmutter Cancer Center and an investigator for the trial, said in a press release. “Typically, these patients are frail, suffer from multiple comorbidities beyond their urothelial cancer and are not able to tolerate additional treatment beyond immunotherapy, leading many to discontinue therapy altogether.”

The EV-201 trial is evaluating enfortumab vedotin-ejfv for patients with locally advanced or metastatic urothelial cancer who have been previously treated with a PD-1 or PD-L1 inhibitor, including those who have also been treated with a platinum-containing chemotherapy in cohort 1 and those who have not received a platinum-containing chemotherapy in this setting and who are ineligible for cisplatin in cohort 2. Overall, 128 patients were enrolled in cohort 1 and 91 patients were enrolled in cohort 2 at multiple centers internationally.

The primary end point for the study is confirmed ORR per blinded independent central review. Key secondary endpoints include assessments of duration of response, disease control rate, progression-free survival (PFS), overall survival (OS), safety, and tolerability.

Enfortumab vedotin-ejfv is a first-in-class ADC directed against Nectin-4, a protein located on the surface of cells and highly expressed in bladder cancer. The FDA granted accelerated approval to the agent in 2019 based on results from the first cohort in this trial.

“This is the first trial to report objective responses in patients with advanced urothelial cancer who had previously received immunotherapy but were ineligible for cisplatin in this setting due to inadequate kidney function or other conditions,” Roger Dansey, MD, chief medical officer at Seagen, said in the release. “These promising new data from EV-201 may support a regulatory application to extend use of [enfortumab vedotin-ejfv] in US patients whose cancer has progressed after immunotherapy and who are ineligible for cisplatin.”

Enfortumab vedotin-ejfv was approved by the FDA in December 2019 and is currently indicated for the treatment of adult patients with locally advanced or metastatic urothelial cancer who have previously received a PD-1 or PD-L1 inhibitor and a platinum-containing chemotherapy before or after surgery or in a locally advanced or metastatic setting. The agent was approved under the FDA’s accelerated approval program based on tumor response rate, however continued approval for this indication may be dependent upon verification and description of clinical benefit in confirmatory trials.

Reference:

Seagen and Astellas Announce Positive Topline Results from Second Cohort of Patients in Phase 2 Pivotal Trial of PADCEV® (enfortumab vedotin-ejfv) in Advanced Urothelial Cancer [news release]. Bothell, Washington & Tokyo. Published October 12, 2020. Accessed October 12, 2020. https://investor.seagen.com/press-releases/news-details/2020/Seagen-and-Astellas-Announce-Positive-Topline-Results-from-Second-Cohort-of-Patients-in-Phase-2-Pivotal-Trial-of-PADCEV-enfortumab-vedotin-ejfv-in-Advanced-Urothelial-Cancer/default.aspx