The results from the second cohort of patients in the pivotal phase 2 single-arm clinical trial known as EV-201, were presented.
The cohort is evaluating the antibody-drug conjugate Enfortumab vedotin ( Enfortumab vedotin-ejfv; Padcev ) for patients with locally advanced or metastatic urothelial cancer who have been previously treated with a PD-1/L1 inhibitor and have not received a Platinum-containing chemotherapy and are ineligible for Cisplatin.
The results have shown a 52% objective response rate ( ORR ) [ 95% Confidence Interval ( CI ): 40.8, 62.4 ] per blinded independent central review and a median duration of response of 10.9 months.
The most frequently reported treatment-related adverse events grade 3 or greater that occurred in more than 5% of patients were: neutropenia, rash, fatigue, increased lipase, diarrhea, decreased appetite, anemia and hyperglycemia.
Enfortumab vedotin is a first-in-class antibody-drug conjugate ( ADC ) that is directed against nectin-4, a protein located on the surface of cells and highly expressed in bladder cancer.
Advanced urothelial cancer in patients who have received immunotherapy and are ineligible for Cisplatin is a particularly difficult disease to treat. 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.
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.
The EV-201 trial is a single-arm, pivotal phase 2 clinical trial of Enfortumab vedotin 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 ( cohort 1 ) and those who have not received a Platinum-containing chemotherapy in this setting and who are ineligible for Cisplatin ( cohort 2 ).
The trial enrolled 128 patients in cohort 1 and 91 patients in cohort 2 at multiple centers internationally.
The primary endpoint is confirmed objective response rate per blinded independent central review. Secondary endpoints include assessments of duration of response, disease control rate, progression-free survival, overall survival, safety and tolerability.
Padcev was approved by the U.S. Food and Drug Administration ( FDA ) in December 2019 and is indicated for the treatment of adult patients with locally advanced or metastatic urothelial cancer who have previously received a programmed death receptor-1 ( PD-1 ) or programmed death-ligand 1 ( PD-L1 ) inhibitor and a Platinum-containing chemotherapy before ( neoadjuvant ) or after ( adjuvant ) surgery or in a locally advanced or metastatic setting.
Urothelial cancer is the most common type of bladder cancer ( 90% of cases ), and can also be found in the urothelial cells that line the renal pelvis, ureter and urethra.
Globally, approximately 580,000 people will be diagnosed with bladder cancer in 2020, and bladder cancer will be attributed to approximately 210,000 deaths worldwide. ( Xagena )
Source: Seagen, 2020