The drug combination demonstrated a 64.5% confirmed objective response rate in individuals with unresectable locally advanced or metastatic urothelial cancer who are ineligible to receive cisplatin-based chemotherapy.
Enfortumab vedotin-ejfv (Padcev; Seagan, Astellas Pharma) in combination with pembrolizumab (Keytruda; Merck) met the primary endpoint of the KEYNOTE-869 study Cohort K, demonstrating a 64.5% confirmed objective response rate (ORR) in patients with unresectable locally advanced or metastatic urothelial cancer (la/mUC) who are ineligible to receive cisplatin-based chemotherapy. The results were evaluated in a blinded independent central review.
Enfortumab vedotin is a first-in-class antibody drug conjugate that is directed against Nectin-4, a protein located on the surface of calls and expressed in bladder cancer.
“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 a statement. “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 median duration of response (DOR) was not yet reached in the trial. The most frequently reported treatment-emergent adverse events occurring in more than 5% of patients that were grade 3 or greater included rash maculo-papular, anemia, increased lipase, urinary tract infection fatigue, diarrhea, and chronic kidney disease.
Overall, the findings were consistent with previously reported efficacy and safety results of the EV-103 dose-escalation cohort and expansion Cohort A.
“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 CEO and chief medical officer at Seagen, said in the statement.
EV-103 Cohort K is aimed at investigating enfortumab vedotin alone or in combination with pembrolizumab as first-line treatment for those with unresectable la/mUC who are ineligible to receive cisplatin-based chemotherapy.
Cohort K is made up of 73 individuals who are on enfortumab vedotin alone and 76 individuals who are taking the enfortumab vedotin with pembrolizumab. The enfortumab vedotin-only arm is intended to characterize the activity of the drug alone for this patient population.
Secondary endpoints include ORR per investigator assessment, DOR, disease control rate, and progression-free survival by blinded independent central review and investigator assessment, overall survival, and assessment of safety.
Seagan, Astellas, and Merck are currently investigating the drug combination as part of an extensive collaboration, which also includes 3 phase 3 studies: EV-302/KEYNOTE-A39, which is intended to confirm the results, and EV-304/KEYNOTE-B15 and EV-303/KEYNOTE-905, which will evaluate the combination in muscle-invasive bladder cancer.
In February 2020, the FDA granted breakthrough therapy designation for enfortumab vedotin in combination with pembrolizumab for individuals with unresectable la/mUC in the first-line setting who cannot receive cisplatin-based chemotherapy. The designation is based on results from the dose-escalation cohort and expansion Cohort A of the phase 1b/2 trial, EV-103, which evaluated this patient population.
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. Seagan. July 26, 2022. Accessed July 26, 2022. https://investor.seagen.com/press-releases/news-details/2022/Seagen-and-Astellas-Announce-Positive-Topline-Results-For-PADCEV-enfortumab-vedotin-ejfv-with-KEYTRUDA-pembrolizumab-as-First-Line-Treatment-for-Advanced-Urothelial-Cancer/default.aspx