Key bladder cancer data pave way for Seattle Genetics to submit marketing application for armed antibody
Seattle Genetics is one step closer to getting its second armed antibody across the finish line, after the ‘breakthrough’ Astellas-partnered drug — enfortumab vedotin — helped patients with advanced or metastatic urothelial cancer, whose disease progressed despite treatment with both platinum-containing chemotherapy and a checkpoint inhibitor, in a key study.
The drug induced a 44% objective response rate (ORR) in 128 patients — and although detailed results from the single-arm EV-201 study will be revealed at a later date, the data are compelling enough for Seattle to submit a US marketing application for the antibody drug conjugate (ADC), the company said on Thursday. A late-stage trial designed to confirm the drug’s safety and efficacy in this patient population is ongoing.
ADCs are a class of therapeutics in which a cancer-killing toxin is attached to a specific antibody using a biodegradable linker. Designed to minimize the effects of the chemotherapy on healthy cells while maximizing tumour cell death, the technology is sometimes likened to a trojan horse as it is engineered to go unnoticed, delivering chemotherapies to cells expressing the antigen target. Seattle Genetics $SGEN already has one ADC on the market, Adcetris, and a slate of others in development.
Enfortumab vedotin (EV) targets Nectin-4, a cell adhesion molecule identified as an ADC target by Astellas. The experimental ADC is also being tested for use in newly diagnosed patients with locally advanced or metastatic urothelial cancer in combination with Keytruda and/or platinum chemotherapy.
The drug continues to be evaluated in the two cohort EV-201 trial: in patients with locally advanced or metastatic urothelial cancer that have been previously treated with a PD-1 or PD-L1 inhibitor, including those who have also been given platinum-based chemotherapy (cohort 1); and those who have not received a platinum-containing chemotherapy and are ineligible for the chemotherapy cisplatin (cohort 2).
In the previous phase I trial, EV generated ORR of of 45%, with a median duration of response (DOR) of 7.5 months in the checkpoint experienced population, SVB Leerink analyst Andrew Berens noted. “Based on the top-line data announced…we believe that EV has sufficiently cleared the bar needed to obtain accelerated approval, which we view as a 20-25% ORR with median DOR of ~5.5 months.”
Urothelial cancer is the most common type of bladder cancer. About 80,470 new cases of bladder cancer are expected to be diagnosed this year, and it is anticipated 17,670 bladder cancer deaths will occur in 2019, according to American Cancer Society estimates. Data suggest most patients do not respond to checkpoint inhibitors after a platinum-containing therapy has failed as an initial treatment for advanced disease, and there are no other approved options for patients once these two lines of treatment have been exhausted.