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Results from the phase 3 EV-301 trial were presented at 2021 American Society of Clinical Oncology Genitourinary Cancers Symposium ( ASCO GU ), and published in The New England Journal of Medicine ( NEJM ).

EV-301 trial is comparing Enfortumab vedotin ( Enfortumab vedotin-ejfv; Padcev ) to chemotherapy in adult patients with locally advanced or metastatic urothelial cancer who were previously treated with Platinum-based chemotherapy and a PD-1/L1 inhibitor.

At the time of pre-specified interim analysis, patients who received Enfortumab vedotin in the trial lived a median of 3.9 months longer than those who received chemotherapy.
Median overall survival was 12.9 vs. 9.0 months, respectively ( hazard ratio, HR=0.70 [ 95% CI: 0.56-0.89 ], p=0.001 ).

For patients in the Enfortumab vedotin arm of the trial, maculopapular rash, fatigue and decreased neutrophil count were the most frequent grade 3 or greater treatment-related adverse events ( TRAEs ) occurring in more than 5% of patients.

Patients who received Enfortumab vedotin in the trial also showed improvement in the following secondary endpoints:

 median progression-free survival, which is the time without progression of cancer, was 5.6 months for Enfortumab vedotin versus 3.7 months for chemotherapy ( HR=0.62 [ 95% CI: 0.51-0.75 ]; p less than 0.00001 );

 overall response rate, the percentage of patients with either complete or partial response, was 40.6% vs 17.9% of patients in the chemotherapy arm ( p less than 0.001 );

 disease control rate ( DCR ), which is the percentage of patients who have achieved complete response, partial response or had stable disease, was 71.9% for Enfortumab vedotin and 53.4% for chemotherapy ( p less than 0.001 ).

Other safety findings included:

 rates of serious TRAEs were comparable between treatment arms ( 23% of patients receiving Enfortumab vedotin vs 23% receiving chemotherapy );

 grade 3 or greater TRAEs were experienced by approximately 50% of patients in both study arms. Grade 3 or greater TRAEs occurring in more than 5% of patients receiving Enfortumab vedotin were maculopapular rash ( occurring in 7% of patients receiving Enfortumab vedotin vs 0% of patients receiving chemotherapy ), fatigue ( 6% vs. 4.5% ) and decreased neutrophil count ( 6% vs 13% ).

The EV-301 trial is a global, multicenter, open-label, randomized phase 3 trial designed to evaluate Enfortumab vedotin versus physician's choice of chemotherapy ( Docetaxel, Paclitaxel or Vinflunine ) in approximately 600 patients with locally advanced or metastatic urothelial cancer who were previously treated with a PD-1/L1 inhibitor and Platinum-based therapies.
The primary endpoint is overall survival and secondary endpoints include progression-free survival, overall response rate, duration of response and disease control rate, as well as assessment of safety / tolerability and quality-of-life parameters.

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.
Nonclinical data suggest the anticancer activity of Enfortumab vedotin is due to its binding to nectin-4 expressing cells followed by the internalization and release of the anti-tumor agent monomethyl auristatin E ( MMAE ) into the cell, which result in the cell not reproducing ( cell cycle arrest ) and in programmed cell death ( apoptosis ).

Urothelial cancer is the most common type of bladder cancer ( 90% of cases ) and can also be found in the renal pelvis, ureter and urethra.
Globally, approximately 549,000 new cases of bladder cancer and 200,000 deaths are reported annually. ( Xagena )

Source: Astellas, 2021

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