Enfortumab Vedotin Plus Pembrolizumab Yield Promising Results in Advanced Urothelial Carcinoma

Results from cohort K of the phase 1b/2 KEYNOTE-896 trial showed improved responses for patients with advanced or metastatic urothelial carcinoma when treated with enfortumab vedotin-efjv plus pembrolizumab.

Promising responses were reported in cohort K of the phase 1b/2 KEYNOTE-896 trial (NCT03288545), which assessed the use of enfortumab vedotin-ejfv (Padcev) plus pembrolizumab (Keytruda) in patients with advanced or metastatic urothelial carcinoma who are not eligible for cisplatin-based therapy, according to a press release from Seagen and Astellas Pharmaceuticals.1

For patients treated with enfortumab plus pembrolizumab, the objective response rate was 64.5% (95% CI, 52.7%-75.1%) and the median duration of response by blinded independent central review was not reached. In cohort K, the most common grade 3 or higher treatment-related adverse effects in 5% or more patients included maculopapular rash, anemia, increased lipase, urinary tract infection, hyperglycemia, and fatigue.

“We are encouraged by the positive topline results of cohort K for the combination of enfortumab vedotin and pembrolizumab in first-line locally advanced or metastatic urothelial cancer, and we look forward to sharing results at an upcoming medical meeting,” Roger Dansey, MD, interim chief executive office and chief medical officer at Seagen, said in the press release.

In cohort K, patients were treated with either enfortumab monotherapy (n = 73) or enfortumab plus pembrolizumab (n = 76) in those with advanced or metastatic urothelial cancer who cannot receive cisplatin-based therapy or who have not received any prior treatment for their disease. In those who received enfortumab alone, it was administered intravenously on days 1 and 8 every 21 days. The combination had a matched dosing regimen, with pembrolizumab being administered on day 1 every 21 days.

Overall, inclusion criteria included having histologically documented advanced or metastatic urothelial cancer, an ECOG performance status of 0 to 2, and being eligible for pembrolizumab. For cohort K specifically, patients must be ineligible for cisplatin-based therapy due to a glomerular filtration rate of less than 60 mL/min and 30 mL/min or more, an ECOG performance status of 2, grade 2 or higher hearing loss, or class 3 heart failure via New York Heart Association classification. Patients must also not have previously received treatment for locally advanced or metastatic disease, as well as no prior adjuvant or neoadjuvant platinum-based therapy within 12 months prior to being enrolled in the trial.

Patients were excluded if they had prior treatment with a PD-1, PD-L1, or PD-2 inhibitor, or prior treatment with stimulatory or co-stimulatory T-cell receptor agents such as CD137 agonists. Patients must also not have grade 2 or higher ongoing sensory or motor neuropathy, active central nervous system metastases, or ongoing clinical toxicity of grade 2 or higher.

“Approximately half of patients with advanced urothelial carcinoma are ineligible for cisplatin-based chemotherapy,” Ahsan Arozullah, MD, MPH, senior vice president and head of Development Therapeutic Areas at Astellas, said in the press release. “We intend to discuss cohort K results with regulatory authorities as we seek to develop a new first-line treatment combination for these patients.”

The FDA has previously granted breakthrough therapy designation in February 2020 for the use of enfortumab plus pembrolizumab in patients who had unresectable advanced or metastatic urothelial carcinoma.2 The designation was based on results from cohort A of the KEYNOTE-896 study, which included patients with unresectable locally advanced or metastatic urothelial cancer who are unable to receive first-line cisplatin-based chemotherapy. Patients received enfortumab intravenously on days 1 and 8 plus pembrolizumab on day 1 of each 21 days cycle.


  1. Seagen and Astellas announce positive topline results for Padcev (enfortumab vedotin-ejfv) with Keytruda (pembrolizumab) as first-line treatment for advanced urothelial cancer. News Release. Seagen and Astellas Pharmaceuticals. July 26, 2022. Accessed July 26, 2022. https://bit.ly/3cLxLEx
  2. FDA grants breakthrough therapy designation to Padcev regimen for advanced bladder cancer. News Release. Seagen. February 19, 2020. Accessed July 26, 2022. https://bit.ly/3oBWBZP