Seattle Genetics' Astellas-partnered ADC nails confirmatory PhIII in urothelial cancer
Nine months after Seattle Genetics nabbed an accelerated approval for its Astellas-partnered antibody-drug conjugate Padcev, the partners said the therapy has nailed a confirmatory Phase III, proving its worth in locally advanced or metastatic urothelial cancer.
Padcev, which has widely been tapped as a potential blockbuster, scored improvements in both overall survival and progression-free survival compared to chemotherapy, causing a 30% reduction in risk of death (p = 0.001) and 39% reduction in risk of disease progression or death (p<0.00001).
The results, which came at an interim analysis, were positive enough for the independent data monitoring committee to recommend stopping the study early. Patients in the chemotherapy arm of the trial will be offered the opportunity to receive PADCEV.
EV-301 builds on EV-201, a single-arm trial involving 125 patients that saw an objective response rate of 44% and a median duration of response for 7.6 months. Targeting the third-line setting or beyond, investigators administered either Padcev or placebo to patients who have progressed after both platinum-based chemotherapy and PD-(L)1 inhibitors.
It’s a tough indication where checkpoint inhibitors like Keytruda and Imfinzi have failed to induce survival benefits, SVB Leerink analyst Andrew Berens noted.
“We also believe Padcev’s overall survival benefit will raise the bar for its competitor Trodelvy, which will present final TROPHY-U-01 results in 3L bladder cancer patients, seeking a potential accelerated approval in 1H21,” he wrote.
Trodelvy, the crown jewel ADC in Gilead’s $21 billion buyout of Immunomedics, has an accelerated approval for metastatic triple-negative breast cancer.
While Trodelvy targets the TROP2 protein, Padcev’s antibody directs the payload to cells with Nectin-4 on their surface. Seattle Genetics will submit its EV-301 data to the FDA in search of a full OK as well as to an upcoming scientific conference.
“We continue to explore Padcev’s activity across the spectrum of urothelial cancer including its potential for use in earlier lines of therapy,” CMO Roger Dansey said in a statement.
Berens estimates $7.8 billion in peak revenue for metastatic bladder cancer when counting frontline as well as refractory or relapsed settings, plus another $1.8 billion in muscle-invasive bladder cancer.