Astellas/Seattle Genetics target advanced bladder cancer with enfortumab vedotin

Roche and Merck & Co have got their respective immunotherapies Tecentriq and Keytruda approved in bladder cancer – but the problem of low response rates remains. At the ASCO annual conference in Chicago researchers highlighted that the responses to these checkpoint inhibitors in urothelial carcinoma are as low as 13%-21%, and most patients will require further therapy due to lack of response or progression. Enter Seattle Genetics and Astellas, who are jointly developing enfortumab vedotin, an antibody-drug conjugate intended as an option for patients whose disease has progressed despite treatment with platinum therapy and the checkpoint inhibitors. Enfortumab vedotin targets Nectin-4, a therapeutic target highly expressed in multiple solid tumours, and like most other antibody-drug conjugates it works by delivering a toxic payload to cancer cells after locking onto the antigen. The aim is to deliver a toxic payload to cancer cells, while leaving healthy cells unaffected. The results discussed at ASCO were from one cohort of the EV-201 trial, where patients had been treated with platinum chemo and PD-1/PD-L1 checkpoint inhibitor. Results at this stage show a 44% response rate and a complete response of 12% and 7.6 months median duration of response. These latest data show a median progression-free survival of 5.8 months, and a median overall survival of 11.7 months. Responses were observed across all subgroups and were irrespective of response to PD-1/L1. Daniel Petrylak, study author presenting the results, a professor of urology at Yale, said the results were strong enough to support an accelerated approval. He noted that there were some side effects, the most common being a rash, adding that they were all reversible. This would involve the FDA granting a conditional licence that would be confirmed by a larger phase 3 study,  EV-301, which is ongoing. Concluding, Petrylak said enfortumab vedotin “has the potential to become a new standard of care in patients who have progressed after platinum and PD/L1 inhibitors”, a view that was also backed by ASCO’s panel of experts at a press briefing. The FDA has already earmarked enfortumab vedotin as a Breakthrough Therapy, clearing the way for a potential fast six-month review after a filing slated for later this year.